JP2018503832A - 眼疾患を有する対象の治療に有用なバイオマーカー - Google Patents
眼疾患を有する対象の治療に有用なバイオマーカー Download PDFInfo
- Publication number
- JP2018503832A JP2018503832A JP2017544573A JP2017544573A JP2018503832A JP 2018503832 A JP2018503832 A JP 2018503832A JP 2017544573 A JP2017544573 A JP 2017544573A JP 2017544573 A JP2017544573 A JP 2017544573A JP 2018503832 A JP2018503832 A JP 2018503832A
- Authority
- JP
- Japan
- Prior art keywords
- sample
- subject
- level
- disease
- gsh
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 35
- 208000030533 eye disease Diseases 0.000 title claims description 9
- 239000000090 biomarker Substances 0.000 title abstract description 9
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims abstract description 95
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 77
- 201000010099 disease Diseases 0.000 claims abstract description 72
- 238000000034 method Methods 0.000 claims abstract description 66
- 206010064930 age-related macular degeneration Diseases 0.000 claims abstract description 30
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 22
- 206010012688 Diabetic retinal oedema Diseases 0.000 claims abstract description 20
- 201000011190 diabetic macular edema Diseases 0.000 claims abstract description 20
- 208000004644 retinal vein occlusion Diseases 0.000 claims abstract description 19
- 206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 15
- 201000001925 Fuchs' endothelial dystrophy Diseases 0.000 claims abstract description 13
- 208000027073 Stargardt disease Diseases 0.000 claims abstract description 10
- 208000008069 Geographic Atrophy Diseases 0.000 claims abstract description 9
- 239000003963 antioxidant agent Substances 0.000 claims description 66
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 63
- 108010053070 Glutathione Disulfide Proteins 0.000 claims description 61
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 claims description 61
- 239000000523 sample Substances 0.000 claims description 54
- 230000003078 antioxidant effect Effects 0.000 claims description 53
- 210000001742 aqueous humor Anatomy 0.000 claims description 46
- 230000036542 oxidative stress Effects 0.000 claims description 42
- 239000013068 control sample Substances 0.000 claims description 39
- 230000002829 reductive effect Effects 0.000 claims description 39
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 35
- 229910052802 copper Inorganic materials 0.000 claims description 35
- 239000010949 copper Substances 0.000 claims description 35
- 108090000623 proteins and genes Proteins 0.000 claims description 30
- 102000004169 proteins and genes Human genes 0.000 claims description 29
- 239000012472 biological sample Substances 0.000 claims description 25
- 238000005259 measurement Methods 0.000 claims description 23
- 208000001491 myopia Diseases 0.000 claims description 20
- 230000004379 myopia Effects 0.000 claims description 20
- 238000003556 assay Methods 0.000 claims description 19
- 230000003247 decreasing effect Effects 0.000 claims description 14
- 238000003018 immunoassay Methods 0.000 claims description 12
- 238000002965 ELISA Methods 0.000 claims description 10
- 238000002967 competitive immunoassay Methods 0.000 claims description 10
- 102000004190 Enzymes Human genes 0.000 claims description 9
- 108090000790 Enzymes Proteins 0.000 claims description 9
- 210000004369 blood Anatomy 0.000 claims description 8
- 239000008280 blood Substances 0.000 claims description 8
- 238000003127 radioimmunoassay Methods 0.000 claims description 8
- 230000030833 cell death Effects 0.000 claims description 5
- 230000004520 agglutination Effects 0.000 claims description 4
- 238000007818 agglutination assay Methods 0.000 claims description 4
- 239000011324 bead Substances 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 238000005516 engineering process Methods 0.000 claims description 4
- 238000002875 fluorescence polarization Methods 0.000 claims description 4
- 239000004816 latex Substances 0.000 claims description 4
- 229920000126 latex Polymers 0.000 claims description 4
- 230000036963 noncompetitive effect Effects 0.000 claims description 4
- 230000002250 progressing effect Effects 0.000 claims description 4
- 238000001262 western blot Methods 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 238000012544 monitoring process Methods 0.000 claims description 3
- 230000004402 high myopia Effects 0.000 claims description 2
- 238000002649 immunization Methods 0.000 claims description 2
- 230000003053 immunization Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 abstract description 6
- 230000003647 oxidation Effects 0.000 abstract description 4
- 230000001568 sexual effect Effects 0.000 abstract 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 114
- 229960003180 glutathione Drugs 0.000 description 54
- 235000006708 antioxidants Nutrition 0.000 description 51
- 210000002966 serum Anatomy 0.000 description 37
- 239000003814 drug Substances 0.000 description 27
- 235000018102 proteins Nutrition 0.000 description 27
- 230000004792 oxidative damage Effects 0.000 description 23
- 239000000203 mixture Substances 0.000 description 21
- 229940079593 drug Drugs 0.000 description 20
- 102100027186 Extracellular superoxide dismutase [Cu-Zn] Human genes 0.000 description 19
- 101000836222 Homo sapiens Extracellular superoxide dismutase [Cu-Zn] Proteins 0.000 description 19
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 19
- 229940118019 malondialdehyde Drugs 0.000 description 18
- 150000001875 compounds Chemical class 0.000 description 16
- 208000024891 symptom Diseases 0.000 description 15
- 210000001525 retina Anatomy 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 12
- 230000001225 therapeutic effect Effects 0.000 description 11
- 210000001519 tissue Anatomy 0.000 description 11
- 206010061818 Disease progression Diseases 0.000 description 10
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 10
- 230000005750 disease progression Effects 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 239000002953 phosphate buffered saline Substances 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 238000002835 absorbance Methods 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- -1 superoxide radicals Chemical class 0.000 description 9
- 238000002560 therapeutic procedure Methods 0.000 description 9
- 230000000007 visual effect Effects 0.000 description 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 8
- 230000002207 retinal effect Effects 0.000 description 8
- 230000008859 change Effects 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 108010024636 Glutathione Proteins 0.000 description 6
- 238000000692 Student's t-test Methods 0.000 description 6
- 108010021188 Superoxide Dismutase-1 Proteins 0.000 description 6
- 102000008221 Superoxide Dismutase-1 Human genes 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000009266 disease activity Effects 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000001301 oxygen Substances 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000012086 standard solution Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 208000011580 syndromic disease Diseases 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 201000004569 Blindness Diseases 0.000 description 5
- XJLXINKUBYWONI-NNYOXOHSSA-N NADP zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-N 0.000 description 5
- 230000034994 death Effects 0.000 description 5
- 230000004438 eyesight Effects 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 5
- JVJFIQYAHPMBBX-UHFFFAOYSA-N 4-hydroxynonenal Chemical compound CCCCCC(O)C=CC=O JVJFIQYAHPMBBX-UHFFFAOYSA-N 0.000 description 4
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 4
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 4
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 4
- 230000006851 antioxidant defense Effects 0.000 description 4
- 235000010323 ascorbic acid Nutrition 0.000 description 4
- 239000011668 ascorbic acid Substances 0.000 description 4
- 229960005070 ascorbic acid Drugs 0.000 description 4
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 4
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 4
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 4
- 230000007547 defect Effects 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 230000003834 intracellular effect Effects 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- 238000012014 optical coherence tomography Methods 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- 150000003254 radicals Chemical class 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- UJCHIZDEQZMODR-BYPYZUCNSA-N (2r)-2-acetamido-3-sulfanylpropanamide Chemical compound CC(=O)N[C@@H](CS)C(N)=O UJCHIZDEQZMODR-BYPYZUCNSA-N 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000002367 Retinal Perforations Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 229960004308 acetylcysteine Drugs 0.000 description 3
- 229940087168 alpha tocopherol Drugs 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 235000005911 diet Nutrition 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 229920002521 macromolecule Polymers 0.000 description 3
- 208000029233 macular holes Diseases 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 230000035772 mutation Effects 0.000 description 3
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
- 230000004297 night vision Effects 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 210000000880 retinal rod photoreceptor cell Anatomy 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 229960000984 tocofersolan Drugs 0.000 description 3
- 230000004393 visual impairment Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000002076 α-tocopherol Substances 0.000 description 3
- 235000004835 α-tocopherol Nutrition 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 2
- CPKVUHPKYQGHMW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;molecular iodine Chemical compound II.C=CN1CCCC1=O CPKVUHPKYQGHMW-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 2
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 238000008157 ELISA kit Methods 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 2
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 208000001140 Night Blindness Diseases 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- 102000003992 Peroxidases Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920000153 Povidone-iodine Polymers 0.000 description 2
- 201000007737 Retinal degeneration Diseases 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 102000019197 Superoxide Dismutase Human genes 0.000 description 2
- 108010012715 Superoxide dismutase Proteins 0.000 description 2
- 102100032891 Superoxide dismutase [Mn], mitochondrial Human genes 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 101000654530 Tupaia virus (isolate Tupaia/Thailand/-/1986) Small hydrophobic protein Proteins 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 210000002159 anterior chamber Anatomy 0.000 description 2
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000002738 chelating agent Substances 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 229960001305 cysteine hydrochloride Drugs 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 229960001484 edetic acid Drugs 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 229940045883 glutathione disulfide Drugs 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 208000017532 inherited retinal dystrophy Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000007912 intraperitoneal administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 2
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 2
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 2
- 150000002978 peroxides Chemical class 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000001766 physiological effect Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229960001621 povidone-iodine Drugs 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 239000000473 propyl gallate Substances 0.000 description 2
- 235000010388 propyl gallate Nutrition 0.000 description 2
- 229940075579 propyl gallate Drugs 0.000 description 2
- 230000003716 rejuvenation Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 2
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 229940001584 sodium metabisulfite Drugs 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 230000003595 spectral effect Effects 0.000 description 2
- 239000012089 stop solution Substances 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 108010045815 superoxide dismutase 2 Proteins 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 230000004304 visual acuity Effects 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- AGBQKNBQESQNJD-SSDOTTSWSA-N (R)-lipoic acid Chemical compound OC(=O)CCCC[C@@H]1CCSS1 AGBQKNBQESQNJD-SSDOTTSWSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000927985 Argis Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010011033 Corneal oedema Diseases 0.000 description 1
- 229910017518 Cu Zn Inorganic materials 0.000 description 1
- 229910017752 Cu-Zn Inorganic materials 0.000 description 1
- 229910017943 Cu—Zn Inorganic materials 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 206010011878 Deafness Diseases 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000004263 Glutamate-Cysteine Ligase Human genes 0.000 description 1
- 108010081687 Glutamate-cysteine ligase Proteins 0.000 description 1
- 108010036164 Glutathione synthase Proteins 0.000 description 1
- 102100034294 Glutathione synthetase Human genes 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000001344 Macular Edema Diseases 0.000 description 1
- 206010025415 Macular oedema Diseases 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- WVVOBOZHTQJXPB-UHFFFAOYSA-N N-anilino-N-nitronitramide Chemical compound [N+](=O)([O-])N(NC1=CC=CC=C1)[N+](=O)[O-] WVVOBOZHTQJXPB-UHFFFAOYSA-N 0.000 description 1
- 102000004722 NADPH Oxidases Human genes 0.000 description 1
- 108010002998 NADPH Oxidases Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 108050001704 Opsin Proteins 0.000 description 1
- 208000003435 Optic Neuritis Diseases 0.000 description 1
- 206010061323 Optic neuropathy Diseases 0.000 description 1
- 206010033546 Pallor Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108700020962 Peroxidase Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 244000299461 Theobroma cacao Species 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 208000014769 Usher Syndromes Diseases 0.000 description 1
- 206010057469 Vascular stenosis Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 208000034698 Vitreous haemorrhage Diseases 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- TVZPLCNGKSPOJA-UHFFFAOYSA-N copper zinc Chemical compound [Cu].[Zn] TVZPLCNGKSPOJA-UHFFFAOYSA-N 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 201000004778 corneal edema Diseases 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000004300 dark adaptation Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 210000002555 descemet membrane Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000002571 electroretinography Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000000871 endothelium corneal Anatomy 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 231100000040 eye damage Toxicity 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 150000003278 haem Chemical class 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000010370 hearing loss Effects 0.000 description 1
- 231100000888 hearing loss Toxicity 0.000 description 1
- 208000016354 hearing loss disease Diseases 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 150000002432 hydroperoxides Chemical class 0.000 description 1
- 238000003317 immunochromatography Methods 0.000 description 1
- 239000003547 immunosorbent Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 210000003093 intracellular space Anatomy 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000004301 light adaptation Effects 0.000 description 1
- 210000001232 limbus corneae Anatomy 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- 238000002690 local anesthesia Methods 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
- 231100000864 loss of vision Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 208000038015 macular disease Diseases 0.000 description 1
- 201000010230 macular retinal edema Diseases 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000006082 mold release agent Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000005043 peripheral vision Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- CMFNMSMUKZHDEY-UHFFFAOYSA-M peroxynitrite Chemical compound [O-]ON=O CMFNMSMUKZHDEY-UHFFFAOYSA-M 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 239000008055 phosphate buffer solution Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 210000000608 photoreceptor cell Anatomy 0.000 description 1
- 108091008695 photoreceptors Proteins 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 238000013310 pig model Methods 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 108091033319 polynucleotide Proteins 0.000 description 1
- 102000040430 polynucleotide Human genes 0.000 description 1
- 239000002157 polynucleotide Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 230000004800 psychological effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 230000004258 retinal degeneration Effects 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 230000004243 retinal function Effects 0.000 description 1
- 239000000790 retinal pigment Substances 0.000 description 1
- 210000001957 retinal vein Anatomy 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 125000001554 selenocysteine group Chemical group [H][Se]C([H])([H])C(N([H])[H])C(=O)O* 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 230000000192 social effect Effects 0.000 description 1
- 229940100996 sodium bisulfate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940001482 sodium sulfite Drugs 0.000 description 1
- 210000001082 somatic cell Anatomy 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 230000037072 sun protection Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 238000012762 unpaired Student’s t-test Methods 0.000 description 1
- 238000011870 unpaired t-test Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y115/00—Oxidoreductases acting on superoxide as acceptor (1.15)
- C12Y115/01—Oxidoreductases acting on superoxide as acceptor (1.15) with NAD or NADP as acceptor (1.15.1)
- C12Y115/01001—Superoxide dismutase (1.15.1.1)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
- G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
- G01N33/6827—Total protein determination, e.g. albumin in urine
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/902—Oxidoreductases (1.)
- G01N2333/90283—Oxidoreductases (1.) acting on superoxide radicals as acceptor (1.15)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/16—Ophthalmology
- G01N2800/164—Retinal disorders, e.g. retinopathy
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/56—Staging of a disease; Further complications associated with the disease
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/70—Mechanisms involved in disease identification
- G01N2800/7004—Stress
- G01N2800/7009—Oxidative stress
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Analytical Chemistry (AREA)
- General Physics & Mathematics (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Pathology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Ophthalmology & Optometry (AREA)
- Biophysics (AREA)
- Bioinformatics & Computational Biology (AREA)
- Toxicology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
ROOR1+電子ドナー(2e−)+2H+→ROH+R1OHの形態の反応を通常触媒する酵素の大きなファミリーである。
Claims (22)
- 酸化的ストレスに関連した眼疾患の重症度を定量又は段階分けするための方法であって、
a)対象から生物学的試料を入手するステップ、
b)対照生物学的試料を提供するステップ、
c)a)及びb)の前記試料中における、銅還元抗酸化能、GSH/GSSG比及びカルボニル付加物レベルの1又は2以上を測定するステップ、
d)前記対象の前記試料中におけるc)の前記1又は2以上の測定値を前記対照試料と比較するステップ、並びに
e)銅還元抗酸化能の前記レベル及び/若しくはGSH/GSSG比が前記対照試料よりも低い場合、並びに/又はカルボニル付加物レベルの前記レベルが前記対照試料よりも高い場合、段階が進行している、又は重症度が上昇しているものとして、前記対象における疾患の重症度を定量又は段階分けするステップを含む、前記方法。 - 試料が、対象の目の眼房水に由来する、請求項1に記載の方法。
- 試料が、対象の目の血液又は血漿に由来する、請求項1に記載の方法。
- 眼疾患が、網膜色素変性症、加齢性黄斑変性症、糖尿病性網膜症、近視、強度近視、フックスジストロフィー、糖尿病性黄斑浮腫(DME)、地図状萎縮、シュタルガルト病、又は網膜静脈閉塞症(RVO)のうちの少なくとも1つから選択される、請求項1に記載の方法。
- 網膜色素変性症、加齢性黄斑変性症、糖尿病性網膜症、又はフックスジストロフィーから選択される疾患を有する対象を治療するための方法であって、
a)前記対象から生物学的試料を入手するステップ、
b)対照生物学的試料を提供するステップ、
c)a)及びb)の前記試料中における、銅還元抗酸化能、GSH/GSSG比及びカルボニル付加物レベルの1又は2以上を測定するステップ、
d)前記対象の前記試料中におけるc)の前記1又は2以上の測定値を前記対照試料と比較するステップ、
e)銅還元抗酸化能の前記レベル及び/若しくはGSH/GSSG比が前記対照試料よりも低い場合、並びに/又はカルボニル付加物レベルの前記レベルが前記対照試料よりも高い場合、段階が進行している、又は重症度が上昇しているものとして、前記対象における前記疾患の重症度を定量又は段階分けするステップ、並びに
f)e)で示された疾患の前記段階又は重症度に基づいて、前記対象における前記疾患のための治療のコースを選択するステップを含む、前記方法。 - 試料が、対象の目の眼房水に由来する、請求項4に記載の方法。
- 試料が、対象の目の血液又は血漿に由来する、請求項4に記載の方法。
- 網膜色素変性症、加齢性黄斑変性症、糖尿病性網膜症、近視、強度近視、フックスジストロフィー、糖尿病性黄斑浮腫(DME)、地図状萎縮、シュタルガルト病、又は網膜静脈閉塞症(RVO)を有する対象の治療をモニターするための方法であって、
a)前記対象から生物学的試料を入手するステップ、
b)対照生物学的試料を提供するステップ、
c)a)及びb)の前記試料中における、銅還元抗酸化能、GSH/GSSG比、カルボニル付加物レベルの1又は2以上を測定するステップ;
d)前記対象の前記試料中におけるc)の前記1又は2以上の測定値を前記対照試料と比較するステップ、
e)前記対象における疾患の段階又は重症度を判定するステップであって、銅還元抗酸化能の前記レベル及び/若しくはGSH/GSSG比が前記対照試料よりも低い場合、並びに/又はカルボニル付加物レベルの前記レベルが前記対照試料よりも高い場合、前記疾患の段階が進行しているか、又は重症度が上昇していると同定され、或いは、銅還元抗酸化能の前記レベル及び/若しくはGSH/GSSG比が前記対照試料よりも高い場合、並びに/又はカルボニル付加物レベルの前記レベルが前記対照試料よりも低い場合、前記疾患の段階が後退しているか、又は網膜色素変性症、加齢性黄斑変性症、糖尿病性網膜症、若しくはフックスジストロフィーの重症度が低減していると同定される、ステップ;
f)e)で示された疾患の前記段階又は重症度に基づいて、前記対象における前記疾患のための治療のコースを選択するステップ、並びに
g)前記治療のコースを前記対象に投与した後、ステップを1又は2回以上反復するステップを含む、前記方法。 - 試料が、対象の目の眼房水に由来する、請求項7に記載の方法。
- 試料が、対象の目の血液又は血漿に由来する、請求項7に記載の方法。
- 酸化的ストレスを定量するための方法であって、
a)対象から生物学的試料を入手するステップ、
b)対照生物学的試料を提供するステップ、
c)a)及びb)の前記試料中における、銅還元抗酸化能、GSH/GSSG比及びカルボニル付加物レベルの1又は2以上を測定するステップ、並びに
d)前記対象の前記試料中におけるc)の前記1又は2以上の測定値を前記対照試料と比較するステップ
を含み、
カルボニル付加物レベルの増加、GSSGに対するGSHの比の低下、及び/又は銅抗酸化能の低下が、酸化的ストレスの指標である、前記方法。 - 試料が、対象の目の眼房水に由来する、請求項10に記載の方法。
- 試料が、対象の目の血液又は血漿に由来する、請求項10に記載の方法。
- 試料が、網膜色素変性症、加齢性黄斑変性症、糖尿病性網膜症、近視、強度近視、フックスジストロフィー、糖尿病性黄斑浮腫(DME)、地図状萎縮、シュタルガルト病、又は網膜静脈閉塞症(RVO)を有することが疑われる対象から得られる、請求項10に記載の方法。
- タンパク質カルボニルレベルのレベルが、EIA(酵素免疫測定法)、ELISA(酵素結合免疫吸着測定法)、RIA(放射性免疫測定法)、間接競合免疫アッセイ、直接競合免疫アッセイ、非競合免疫アッセイ、サンドイッチ免疫アッセイ、凝集アッセイ、ウェスタンブロットアッセイ、スロットブロットアッセイ、蛍光偏光法、ラテックス凝集、ラテラルフローアッセイ、免疫クロマトグラフィーアッセイ、免疫チップ、ディップスティック免疫試験、又はビースをベースにした技術によって測定される、請求項10に記載の方法。
- カルボニル付加物レベルの増加、GSSGに対するGSHの比の低下及び/又は銅抗酸化能の低下が対象における酸化的ストレスの指標であるという知見に基づいて錐体細胞死を測定するステップをさらに含む、請求項10に記載の方法。
- 目の酸化的ストレスを測定するためのキットであって、
a)対象の生物学的試料のための第1の容器、
b)対照生物学的試料のための第2の容器、
c)a)及びb)の前記試料中における銅還元抗酸化能、GSH/GSSG比及びカルボニル付加物レベルを測定するための試薬を含む1又は2以上のバイアル、並びに
d)前記対象の前記試料中におけるc)の前記1又は2以上の測定値を前記対照試料と比較するための指示書
を含み、カルボニル付加物レベルの増加、GSSGに対するGSHの比の低下、及び/又は銅抗酸化能の低下が酸化的ストレスの指標である、前記キット。 - 試料が、対象の目の眼房水に由来する、請求項16に記載のキット。
- 生物学的試料が、網膜色素変性症、加齢性黄斑変性症、糖尿病性網膜症、近視、強度近視、フックスジストロフィー、糖尿病性黄斑浮腫(DME)、地図状萎縮、シュタルガルト病、又は網膜静脈閉塞症(RVO)を有することが疑われる対象に由来する、請求項16に記載のキット。
- タンパク質カルボニルレベルが、EIA(酵素免疫測定法)、ELISA(酵素結合免疫吸着測定法)、RIA(放射性免疫測定法)、間接競合免疫アッセイ、直接競合免疫アッセイ、非競合免疫アッセイ、サンドイッチ免疫アッセイ、凝集アッセイ、ウェスタンブロットアッセイ、スロットブロットアッセイ、蛍光偏光法、ラテックス凝集、ラテラルフローアッセイ、免疫クロマトグラフィーアッセイ、免疫チップ、ディップスティック免疫試験、又はビースをベースにした技術によって測定される、請求項16に記載のキット。
- 指示書が、銅還元抗酸化能のレベル及び/若しくはGSH/GSSG比が対照試料よりも低い場合、並びに/又はカルボニル付加物レベルのレベルが前記対照試料よりも高い場合、疾患の段階が進行しているか、又は重症度が上昇していると同定され、或いは銅還元抗酸化能の前記レベル及び/若しくはGSH/GSSG比が前記対照試料よりも高い場合、並びに/又はカルボニル付加物レベルの前記レベルが前記対照試料よりも低い場合、前記疾患が同定され、前記疾患の段階が後退していると見なされるか、又は前記疾患の重症度が低減していると判定するために使用される、請求項16に記載のキット。
- カルボニル付加物レベルの増加、GSSGに対するGSHの比の低下及び/又は銅抗酸化能の低下が、網膜色素変性症における錐体細胞死の指標である、請求項16に記載のキット。
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201462078138P | 2014-11-11 | 2014-11-11 | |
US62/078,138 | 2014-11-11 | ||
US201562188377P | 2015-07-02 | 2015-07-02 | |
US62/188,377 | 2015-07-02 | ||
PCT/US2015/060172 WO2016077467A1 (en) | 2014-11-11 | 2015-11-11 | Biomarkers useful in the treatment of subjects having diseases of the eye |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020082163A Division JP7018470B2 (ja) | 2014-11-11 | 2020-05-07 | 眼疾患を有する対象の治療に有用なバイオマーカー |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2018503832A true JP2018503832A (ja) | 2018-02-08 |
JP2018503832A5 JP2018503832A5 (ja) | 2018-12-13 |
JP6849867B2 JP6849867B2 (ja) | 2021-03-31 |
Family
ID=55954994
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017544573A Active JP6849867B2 (ja) | 2014-11-11 | 2015-11-11 | 眼疾患を有する対象の治療に有用なバイオマーカー |
JP2020082163A Active JP7018470B2 (ja) | 2014-11-11 | 2020-05-07 | 眼疾患を有する対象の治療に有用なバイオマーカー |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020082163A Active JP7018470B2 (ja) | 2014-11-11 | 2020-05-07 | 眼疾患を有する対象の治療に有用なバイオマーカー |
Country Status (4)
Country | Link |
---|---|
US (2) | US11268964B2 (ja) |
EP (1) | EP3218481B1 (ja) |
JP (2) | JP6849867B2 (ja) |
WO (1) | WO2016077467A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2021006519A (ja) * | 2019-06-27 | 2021-01-21 | ペガヴィジョン コーポレーションPegavision Corporation | 角膜修復機能を有する眼科用製品 |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11548851B2 (en) | 2017-09-20 | 2023-01-10 | Nacuity Pharmaceuticals, Inc. | Method for preparation of n-acetyl cysteine amide and derivatives thereof |
US10590073B2 (en) | 2017-09-20 | 2020-03-17 | Nacuity Pharmaceuticals, Inc. | Method for preparation of N-acetyl cysteine amide and derivatives thereof |
US11091433B2 (en) | 2017-09-20 | 2021-08-17 | Nacuity Pharmaceutials, Inc. | Method for preparation of N-acetyl cysteine amide and derivatives thereof |
US20190135741A1 (en) | 2017-11-09 | 2019-05-09 | Nacuity Pharmaceuticals, Inc. | Methods of Making Deuterium-Enriched N-acetylcysteine Amide (D-NACA) and (2R, 2R')-3,3'-Disulfanediyl BIS(2-Acetamidopropanamide) (DINACA) and Using D-NACA and DINACA to Treat Diseases Involving Oxidative Stress |
US11766413B2 (en) | 2019-01-11 | 2023-09-26 | Nacuity Pharmaceuticals, Inc. | Treatment of age-related macular degeneration, glaucoma, and diabetic retinopathy with n-acetylcysteine amide (NACA) or (2R,2R′)-3,3′-disulfanediyl BIS(2-acetamidopropanamide)(DiNACA) |
WO2022167827A1 (en) * | 2021-02-05 | 2022-08-11 | Idec Therapeutic | Composition for controlling and/or preventing oxidative stress comprising at least s-adenosyl methionine and astragalus sp. polysaccharides |
Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3340147A (en) | 1965-06-28 | 1967-09-05 | Mead Johnson & Co | Amides of n-acylated cysteines |
US6420429B1 (en) | 1997-12-23 | 2002-07-16 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Brain targeted low molecular weight hydrophobic antioxidant compounds |
AU2002345699A1 (en) | 2001-06-13 | 2002-12-23 | Webb-Waring Institute For Biomedical Research | A diagnostic and prognostic method for evaluating ocular inflammation and oxidative stress and the treatment of the same |
BE1014949A3 (fr) | 2001-08-14 | 2004-07-06 | Probiox | Procede de detection de stress oxydant et trousse pour sa mise en oeuvre. |
US20060211628A1 (en) | 2002-08-02 | 2006-09-21 | Daphne Atlas | Treatment of multiple sclerosis with brain targeted anti oxidant compounds |
RU2007143040A (ru) | 2005-04-21 | 2009-05-27 | Гленн А. ГОЛДШТЕЙН (US) | Амид n-ацетилцистеина (амид nac) в лечении заболеваний и состояний, связанных с окислительным стрессом |
JP4840804B2 (ja) | 2006-01-20 | 2011-12-21 | 学校法人慶應義塾 | 酸化ストレスの判定方法 |
US20120150029A1 (en) | 2008-12-19 | 2012-06-14 | University Of Miami | System and Method for Detection and Monitoring of Ocular Diseases and Disorders using Optical Coherence Tomography |
WO2011028935A2 (en) | 2009-09-02 | 2011-03-10 | The Regents Of The University Of Colorado | Methods of treating mitochondrial disorders using metalloporhyrins |
US20120142550A1 (en) | 2010-12-06 | 2012-06-07 | Zehnder James L | Vanin 1 as a Peripheral Blood Oxidative Stress Sensor |
ES2384798B1 (es) | 2011-10-19 | 2013-06-04 | Universidad De Granada | Uso de melatonina para el tratamiento y/o prevención de la mucositis. |
US20150148423A1 (en) | 2012-04-26 | 2015-05-28 | Sentient Lifesciences, Inc. | Use of n-acetylcysteine amide in the treatment of disease and injury |
EP3459598A1 (en) * | 2012-12-06 | 2019-03-27 | Stealth Peptides International, Inc. | Combinations of peptide therapeutics and methods for using same |
US20150328337A1 (en) | 2012-12-19 | 2015-11-19 | The Johns Hopkins University | Protection from oxidative damage by gene transfer by glutamate cysteine ligase and glutathione synthase |
WO2015148880A1 (en) | 2014-03-28 | 2015-10-01 | Warner Babcock Institute for Green Chemistry | Method for the preparation of n-acetyl cysteine amide |
CA2967327C (en) | 2014-11-07 | 2020-04-28 | The Johns Hopkins University | Treatment of retinitis pigmentosa with n-acetylcysteine amide |
US11173135B2 (en) | 2016-03-17 | 2021-11-16 | Thiogenesis Therapeutics, Inc. | Compositions for controlled release of cysteamine and systemic treatment of cysteamine sensitive disorders |
-
2015
- 2015-11-11 EP EP15858590.1A patent/EP3218481B1/en active Active
- 2015-11-11 US US15/523,657 patent/US11268964B2/en active Active
- 2015-11-11 WO PCT/US2015/060172 patent/WO2016077467A1/en active Application Filing
- 2015-11-11 JP JP2017544573A patent/JP6849867B2/ja active Active
-
2020
- 2020-05-07 JP JP2020082163A patent/JP7018470B2/ja active Active
-
2022
- 2022-01-24 US US17/582,286 patent/US20220146533A1/en active Pending
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2021006519A (ja) * | 2019-06-27 | 2021-01-21 | ペガヴィジョン コーポレーションPegavision Corporation | 角膜修復機能を有する眼科用製品 |
Also Published As
Publication number | Publication date |
---|---|
EP3218481A4 (en) | 2018-05-30 |
JP6849867B2 (ja) | 2021-03-31 |
WO2016077467A1 (en) | 2016-05-19 |
JP7018470B2 (ja) | 2022-02-10 |
JP2021067668A (ja) | 2021-04-30 |
US20220146533A1 (en) | 2022-05-12 |
US11268964B2 (en) | 2022-03-08 |
EP3218481B1 (en) | 2020-04-08 |
EP3218481A1 (en) | 2017-09-20 |
US20170370945A1 (en) | 2017-12-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7018470B2 (ja) | 眼疾患を有する対象の治療に有用なバイオマーカー | |
Campochiaro et al. | Oral N-acetylcysteine improves cone function in retinitis pigmentosa patients in phase I trial | |
Campochiaro et al. | The mechanism of cone cell death in Retinitis Pigmentosa | |
Chen et al. | Dysfunction of the retinal pigment epithelium with age: increased iron decreases phagocytosis and lysosomal activity | |
Ozkul et al. | Oxidative stress in acute ischemic stroke | |
Chew | Ocular manifestations of von Hippel–Lindau disease: clinical and genetic investigations | |
Miyake et al. | Nepafenac 0.1% versus fluorometholone 0.1% for preventing cystoid macular edema after cataract surgery | |
Li et al. | Hyperglycaemia exacerbates choroidal neovascularisation in mice via the oxidative stress-induced activation of STAT3 signalling in RPE cells | |
Puustjärvi et al. | Plasma and aqueous humour levels of homocysteine in exfoliation syndrome | |
Amaral et al. | 7-Ketocholesterol induces inflammation and angiogenesis in vivo: a novel rat model | |
Yuki et al. | Increased serum total antioxidant status and decreased urinary 8‐hydroxy‐2′‐deoxyguanosine levels in patients with normal‐tension glaucoma | |
Delcourt et al. | Associations of cataract with antioxidant enzymes and other risk factors: the French Age-Related Eye Diseases (POLA) Prospective Study | |
Rödl et al. | Increased homocysteine levels in tear fluid of patients with primary open-angle glaucoma | |
WO2021067823A2 (en) | A new treatment for meibomian gland dysfunction | |
Altinkaynak et al. | A novel marker in acute central serous chorioretinopathy: thiol/disulfide homeostasis | |
Yadav et al. | How accurate are ICD-9 codes for acute (Ap) and chronic (Cp) pancreatitis?-A large VA hospital experience | |
Liu et al. | Ferroptosis Contributes to Microvascular Dysfunction in Diabetic Retinopathy | |
US20170315135A1 (en) | Biomarkers useful in the treatment of subjects having retinits pigmentosa | |
AlKot et al. | Early detection of diabetic retinopathy among type 2 diabetic patients in Qaluobia Governorate, Egypt | |
Mikoluc et al. | Reduced retinol (Vitamin A) and α-tocopherol (Vitamin E) blood levels and increased myeloperoxidase (MPO) activity in Children with High Myopia | |
Yalçınkaya Çakır et al. | Anterior chamber flare and choroidal vascular index as inflammatory markers after uncomplicated phacoemulsification surgery | |
JP2022531484A (ja) | 加齢性黄斑変性症を治療するための物質および方法 | |
Tvenning | Drusenoid pigment epithelial detachments and age-related macular degeneration | |
Cheung et al. | Asia Pac J Ophthalmol (Phila). 2017 Oct 3.[Epub ahead of print] Anti-VEGF Therapy for Neovascular AMD and Polypoidal Choroidal Vasculopathy. | |
Levin et al. | Liposomal delivery of EphA2 siRNA in combination with gemcitabine reduces pancreatic tumor growth and invasion |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20181102 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20181102 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190808 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20190819 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191119 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20200402 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200507 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200507 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6849867 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |