CN104982379A - Method for inducing primate macular degeneration model by high fat - Google Patents
Method for inducing primate macular degeneration model by high fat Download PDFInfo
- Publication number
- CN104982379A CN104982379A CN201510364789.3A CN201510364789A CN104982379A CN 104982379 A CN104982379 A CN 104982379A CN 201510364789 A CN201510364789 A CN 201510364789A CN 104982379 A CN104982379 A CN 104982379A
- Authority
- CN
- China
- Prior art keywords
- parts
- macular degeneration
- primate
- model
- high fat
- 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
- 208000002780 macular degeneration Diseases 0.000 title claims abstract description 44
- 238000000034 method Methods 0.000 title claims abstract description 31
- 241000288906 Primates Species 0.000 title claims abstract description 27
- 230000001939 inductive effect Effects 0.000 title abstract 2
- 241000282414 Homo sapiens Species 0.000 claims abstract description 24
- 230000003203 everyday effect Effects 0.000 claims abstract description 5
- 230000006698 induction Effects 0.000 claims description 19
- 235000013305 food Nutrition 0.000 claims description 18
- 150000002632 lipids Chemical class 0.000 claims description 16
- 206010025421 Macule Diseases 0.000 claims description 8
- 208000024891 symptom Diseases 0.000 claims description 7
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- 244000068988 Glycine max Species 0.000 claims description 6
- 235000010469 Glycine max Nutrition 0.000 claims description 6
- 208000021959 Abnormal metabolism Diseases 0.000 claims description 5
- 240000007594 Oryza sativa Species 0.000 claims description 5
- 235000007164 Oryza sativa Nutrition 0.000 claims description 5
- 235000010627 Phaseolus vulgaris Nutrition 0.000 claims description 5
- 244000046052 Phaseolus vulgaris Species 0.000 claims description 5
- 230000008859 change Effects 0.000 claims description 5
- 230000008021 deposition Effects 0.000 claims description 5
- 235000013312 flour Nutrition 0.000 claims description 5
- 235000012054 meals Nutrition 0.000 claims description 5
- 230000006371 metabolic abnormality Effects 0.000 claims description 5
- 235000009566 rice Nutrition 0.000 claims description 5
- 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 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- 239000002994 raw material Substances 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 claims description 3
- 235000019743 Choline chloride Nutrition 0.000 claims description 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 3
- 235000019733 Fish meal Nutrition 0.000 claims description 3
- 241000287828 Gallus gallus Species 0.000 claims description 3
- 229930003268 Vitamin C Natural products 0.000 claims description 3
- 229930003427 Vitamin E Natural products 0.000 claims description 3
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 claims description 3
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 3
- 229960002079 calcium pantothenate Drugs 0.000 claims description 3
- 229960003178 choline chloride Drugs 0.000 claims description 3
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 claims description 3
- 238000003745 diagnosis Methods 0.000 claims description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 3
- 239000004467 fishmeal Substances 0.000 claims description 3
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 3
- 239000003921 oil Substances 0.000 claims description 3
- 235000019198 oils Nutrition 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 3
- 239000008158 vegetable oil Substances 0.000 claims description 3
- 235000019154 vitamin C Nutrition 0.000 claims description 3
- 239000011718 vitamin C Substances 0.000 claims description 3
- 235000019165 vitamin E Nutrition 0.000 claims description 3
- 229940046009 vitamin E Drugs 0.000 claims description 3
- 239000011709 vitamin E Substances 0.000 claims description 3
- QCVGEOXPDFCNHA-UHFFFAOYSA-N 5,5-dimethyl-2,4-dioxo-1,3-oxazolidine-3-carboxamide Chemical compound CC1(C)OC(=O)N(C(N)=O)C1=O QCVGEOXPDFCNHA-UHFFFAOYSA-N 0.000 claims description 2
- 108010000912 Egg Proteins Proteins 0.000 claims description 2
- 102000002322 Egg Proteins Human genes 0.000 claims description 2
- 235000014103 egg white Nutrition 0.000 claims description 2
- 210000000969 egg white Anatomy 0.000 claims description 2
- 206010064930 age-related macular degeneration Diseases 0.000 abstract description 15
- 241001465754 Metazoa Species 0.000 abstract description 13
- 238000010171 animal model Methods 0.000 abstract description 12
- 208000008069 Geographic Atrophy Diseases 0.000 abstract description 8
- 230000003285 pharmacodynamic effect Effects 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 5
- 238000011156 evaluation Methods 0.000 abstract description 4
- 230000002427 irreversible effect Effects 0.000 abstract description 4
- 238000012216 screening Methods 0.000 abstract description 4
- 230000008506 pathogenesis Effects 0.000 abstract description 3
- 230000002269 spontaneous effect Effects 0.000 abstract description 2
- 208000000208 Wet Macular Degeneration Diseases 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 230000003902 lesion Effects 0.000 abstract 1
- 238000001356 surgical procedure Methods 0.000 abstract 1
- 210000001508 eye Anatomy 0.000 description 28
- 238000013534 fluorescein angiography Methods 0.000 description 10
- 238000012014 optical coherence tomography Methods 0.000 description 9
- 208000000260 Warts Diseases 0.000 description 8
- 210000001525 retina Anatomy 0.000 description 8
- 201000010153 skin papilloma Diseases 0.000 description 8
- 238000002156 mixing Methods 0.000 description 7
- 230000007170 pathology Effects 0.000 description 7
- 210000004204 blood vessel Anatomy 0.000 description 6
- 230000002207 retinal effect Effects 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 208000032436 Retinal depigmentation Diseases 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 210000003161 choroid Anatomy 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 4
- 206010003694 Atrophy Diseases 0.000 description 3
- 241000282693 Cercopithecidae Species 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 206010047571 Visual impairment Diseases 0.000 description 3
- 230000037444 atrophy Effects 0.000 description 3
- 230000001717 pathogenic effect Effects 0.000 description 3
- 239000000049 pigment Substances 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 208000029257 vision disease Diseases 0.000 description 3
- 230000004393 visual impairment Effects 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 2
- 206010039729 Scotoma Diseases 0.000 description 2
- 235000019764 Soybean Meal Nutrition 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 210000005252 bulbus oculi Anatomy 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 210000000981 epithelium Anatomy 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 210000004126 nerve fiber Anatomy 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 210000002445 nipple Anatomy 0.000 description 2
- 230000000474 nursing effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000004455 soybean meal Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 230000004382 visual function Effects 0.000 description 2
- 201000009487 Amblyopia Diseases 0.000 description 1
- 208000031873 Animal Disease Models Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241000282405 Pongo abelii Species 0.000 description 1
- 208000033240 Progressive symmetric erythrokeratodermia Diseases 0.000 description 1
- 208000037111 Retinal Hemorrhage Diseases 0.000 description 1
- 208000027073 Stargardt disease Diseases 0.000 description 1
- 206010047555 Visual field defect Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 238000011558 animal model by disease Methods 0.000 description 1
- 238000012550 audit Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 230000009841 epithelial lesion Effects 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000002189 macula lutea Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000003950 pathogenic mechanism Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 208000027653 severe early-childhood-onset retinal dystrophy Diseases 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/02—Breeding vertebrates
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P60/00—Technologies relating to agriculture, livestock or agroalimentary industries
- Y02P60/80—Food processing, e.g. use of renewable energies or variable speed drives in handling, conveying or stacking
- Y02P60/87—Re-use of by-products of food processing for fodder production
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Environmental Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Zoology (AREA)
- Animal Husbandry (AREA)
- Biodiversity & Conservation Biology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The present invention discloses a method for inducing a primate macular degeneration model by high fat. The method comprises: feeding an inhuman primate suffered from drusen lesion with a high-fat feed and feeding the inhuman primate for three times every day with the feeding amount of 75-100g per time; and feeding the inhuman primate for 60-110 days to obtain a stable macular degeneration model. According to the method disclosed by the present invention, a dry or wet macular degeneration animal model close to spontaneous occurring of human beings can be obtained and the integrity of a Bruch's film can be kept; the model is stable and irreversible, and has good animal obedience; animals do not need to be subjected to surgeries or be killed to be checked; the modeling cost is very low; and an ideal animal model is provided for researching a pathogenesis of the macular degeneration model, screening treatment medicines and carrying out pharmacodynamic evaluation.
Description
Technical field
The present invention relates to a kind of method for building up of animal disease model, particularly relate to a kind of method of high fat induction primate macular degeneration model.
Background technology
Macular degeneration is a kind of chronic ocular disease, the Aging that its pathomechanism is mainly eyes macular area structure changes, be divided into AMD (also known as senile macular degeneration, age-related macular degeneration, ADM) and juvenile macular degeneration two kinds.ADM is the degenerative disease occurring in layer of retina,pigment epithelium, Bruch ' s film, CC, its illness rate increases with the growth at age, in English, Mei Deng developed country, ADM is modal reason in over-65s the elderly diseases causing blindness, along with the quickening of China's aging population, this disease has obvious ascendant trend.ADM is divided into dryness and moist two types, and wherein dryness ADM is also called atrophic or non-exudative AMD, is moistly also called exudative AMD.Dryness AMD feature is Progressive symmetric erythrokeratodermia retinal pigment epithelium atrophy or withered, and cause photosensory cell sex change, cause central amblyopia, eyes are fallen ill simultaneously, and visual impairment is slow.Moist AMD feature is have between retinal pigment epithelium and Bruch ' s film to be formed from choroidal new vessels, serosity and (or) hemorrhagic retinal pigment epithelium and (or) neural epithelium is caused to depart from, the first sequela of eyes, visual impairment is more anxious.Moist ADM patient, due to associated with choroidal new vessels (CNV), often causes macula lutea Repeated Hemorrhage, even more serious to the infringement of patient's visual function.Current ADM is still without clear and definite effective treatment means, ADM pathogenesis and methods for the treatment of become the study hotspot of society, good macular degeneration animal model is set up in the task of top priority, for the study of incident mechanism of this disease, pharmacodynamic study and other translational medicine preclinical studies provide stable model vehicle.
A lot of scientist prepares macular degeneration animal model by multiple method.As induced with laser CNV model, laser, by producing the biological effects such as mechanical damage, fuel factor and photochemistry to retina, causes Bruch ' s film destroy, makes retina produce new vessels in inflammation repair process.Another also have: model gene modifies mouse model, operation induction CNV model etc., but the ADM model provided at present all has the following disadvantages: (1) selects the non-primate such as mouse, rat as model, there is species variation in non-primate and mankind ADM, its eye structure, pathogenic process and pathological characteristic and people exist larger difference; (2) Bruch ' s film is destroyed; (3) too much growth factor is produced.At present, still do not have to simulate the desirable animal model that development occurs macular degeneration in humans completely.
Summary of the invention
For the deficiency that above-mentioned macular degeneration animal model exists, the invention provides a kind of method of high fat induction primate macular degeneration model, the method is to suffer from the non-human primate of glass-film verrucosis change into object, induced by high lipid food, obtain and stablize the irreversible animal model can simulated macular degeneration in humans completely and occur to develop, for the screening, pharmacodynamic evaluation etc. of the pathogenetic research of macular degeneration, medicine provide good model vehicle.
The present invention is achieved by the following technical solutions:
A method for high fat induction primate macular degeneration model, the method, by suffering from the non-human primate of glass-film verrucosis change, is fed with high lipid food, feed 3 every day, each feeding volume is 75-100 gram, feeds 60-110 days, can obtain stable macular degeneration model.
The method of the above high fat induction primate macular degeneration model, in nursing after 60 days, with reference to Human clinical's diagnostic criteria, by color fundus photograph, fundus fluorescein angiography and optical coherence tomography, tracing observation is carried out to non-human primate, observe 1 time weekly, when observing retinal pigment epithelium atrophy or having new vessels to be formed between retinal pigment epithelium and Bruch ' s film, stable macular degeneration model can be obtained.
The method of the above high fat induction primate macular degeneration model, described high lipid food is the high lipid food aiming at primate development, comprises the raw material of following weight part ratio: basal feed 73 parts, lard 26 parts, vegetable oil 24 parts, 2 parts, egg white, sucrose 2 parts; Described basal feed comprises the raw material of following percentage by weight: 570 parts, rice, 80 parts, flour, dregs of beans 150 parts, soybean 45 parts, FSPC 40 parts, fish meal 20 parts, chicken meal 50 parts, 8 parts, soya-bean oil, calcium monohydrogen phosphate 12 parts, Choline Chloride 1.5 parts, Paris white 3.6 parts, calcium pantothenate 0.15 part, salt 3.7 parts, vitamin C 0.2 part, vitamin E 0.1 part.Its preparation method is with reference to the authorized patent of my company: primate test-type high lipid food and preparation method thereof, ZL 201210581731.0.
Glass-film wart is that one occurs in choroid, amphiblestroid a kind of degenerative disease, caused by pigment epithelial cell Specific mefabolites abnormal deposition on the retina, early stage visual function can be without prejudice, some patient occurs that physiologic scotoma expands, also can there is arcuate scotoma in severe patient, visual field constriction or visual impairment.Of the present invention suffer from non-human primate that glass-film verrucosis becomes and refer to have the symptom of abnormal metabolism thing deposition at eyeground Posterior pole or macula area through color fundus photograph diagnosis.
The method of the above high fat induction primate macular degeneration model, described high lipid food is patent.
Macular degeneration, betides more than 45 years old mostly, and its illness rate increases with the growth at age.The method of the above high fat induction primate macular degeneration model, described non-human primate is preferably person in middle and old age's non-human primate, and the age is >=10 years old.
Primate and human gene autoploidy high, immune response is similar to people, in all animals eyeball and physiological and biochemical index the most similar to the mankind, therefore, the present invention selects non-human primate as the animal model of macular degeneration.Described non-human primate, can be ape, monkey, orangutan etc., is preferably machin.
Compared with prior art, the beneficial effect that the present invention obtains is:
(1) the present invention will suffer from the non-human primate of glass-film verrucosis change, naturally induced by the diet of high lipid food, can obtain close to the abiogenous dryness of the mankind or moist fundus macular degeneration animal model, and it is complete to preserve Bruch ' s film, model stability is irreversible, for the screening, pharmacodynamic evaluation etc. of the pathogenetic research of macular degeneration, medicine provide good model vehicle.
(2) high lipid food that the present invention adopts is design for non-human primate specially, containing animal tallow lard in high lipid food formula, also has the vegetable oil of significant proportion simultaneously, in formula, the content of grease is up to 28.8-51.8%, higher than other high lipid foods, containing sucrose in feed, mouthfeel is good, high lipid food only need be put into and take food dish by the person of feeding, animal just can oneself be taken, and has good compliance to it, convenient, easy to operate, can feed for a long time, primate simulating human can be built and to ingest the truly natural biotic habitat of high-fat foods.The high lipid food that the present invention adopts is induced and accelerates the formation of animal macular degeneration model, and after animal feeding 60-110 days, can obtain stablizing irreversible macular degeneration model, the success rate of modeling is more than 90%.
(3) the present invention is by color fundus photograph, fundus fluorescein angiography and optical coherence tomography, check whether non-human primate suffers from glass-film wart, dryness or moist fundus macular degeneration disease, inspection method used is highly sensitive, high specificity, simple to operate, can biopsy, little to animal injury, after obtaining stable macular degeneration model, animal still can carry out pharmacodynamics test.
(4) non-human primate selected of the present invention, high with human gene autoploidy, immune response is similar to people, in all animals eyeball and physiological and biochemical index the most similar to the mankind, the macular degeneration model set up, the generation of its disease, pathologic process and mankind's similarity are very high, can simulate developing of macular degeneration in humans.
Accompanying drawing explanation
Fig. 1 is the machin color fundus photograph figure suffering from glass-film wart
Fig. 2 is the machin fundus fluorescein angiography figure suffering from glass-film wart
Fig. 3 is the color fundus photograph figure of induction machin wet MD eyes
Fig. 4 is the fundus fluorescein angiography figure of induction machin wet MD eyes
Fig. 5 is the optical coherence tomography figure of induction machin wet MD eyes
Fig. 6 is the color fundus photograph figure of induction machin Dry macular degeneration left eye
Fig. 7 is the fundus fluorescein angiography figure of induction machin Dry macular degeneration left eye
Fig. 8 is the optical coherence tomography figure of induction machin Dry macular degeneration left eye
Embodiment
Below in conjunction with specific embodiment, the present invention is further described, but do not limit the scope of the invention and range of application.
One, key instrument, test material
1. key instrument:
(1) fundus camera: buy in Kanggong department of Japanese Top.
(2) OCT somascope: buy in Heidelberg, Germany company.
(3) fluorescence fundus angiography instrument: buy in company of Kanggong department of Japanese Top.
2. test material:
(1) preparation method of basal feed, comprises the following steps:
A. get rice, soybean, dregs of beans, pulverize respectively, cross 60 mesh sieves, the rice meal that must crush, soybean meal, bean cake powder;
B. get vitamin E 0.1kg, soya-bean oil 8kg, mixing, adds flour by equal increments method, and mixing is crossed 60 mesh sieves, obtained finely dispersed flour mixture A;
C. get Choline Chloride 1.5kg, vitamin C 0.2kg, calcium pantothenate 0.15kg, mixing, adds stone flour 3.6kg, mixing, then adds salt 3.7kg, calcium monohydrogen phosphate 12kg, and mixing, obtains mixture B;
D. get soybean meal 45kg, FSPC 40kg, fish meal 20kg, chicken meal 50kg and mixture A, B, mixing, obtains mixture C;
E. get rice meal 570kg, bean cake powder 150kg and mixture C, put in mixer and be uniformly mixed, the baking oven putting into 100 DEG C is dried to moisture≤10%, takes out, to obtain final product.
(2) preparation method of high lipid food, comprises the following steps:
Get lard 26kg, peanut oil 24kg, egg 2kg, sucrose 2kg, stir, mixing, joins in the above-mentioned basal feed prepared of 73kg, then adds suitable quantity of water, stir into uniform biscuit batter, continue to rub and make it to become dough, dough is cut into the blockage of equivalent, the baking box putting into 180 DEG C is dried, take out, to obtain final product.
Two, experimental animal
The machin that this test uses cultivates Breeding Center by the male gloomy primate in Guangxi and provides.Through the quarantine of routine and health check-up, damaged without limbs, animal normal behaviour habit is complete, and audit report comprises clinical examination and laboratory examination content, all performs with reference to national standard.This research completes in Guangxi Nanning Lingkang Senoke Biology Science and Technology Co., Ltd AAALAC (AssociationforAssessment and Accreditation of Laboratory Animal) international qualification certification laboratory.
Machin, through eye-ground photography machine check, is chosen at the machin 18 that eyeground Posterior pole or macula area have the symptom of abnormal metabolism thing deposition, age 10-18 year, wherein 12 female monkeys, 6 public monkeys, and they are divided at random blank group, experimental group, blank group 8, experimental group 10.
Machin (the being numbered 1) color fundus photograph suffering from glass-film wart is shown in Fig. 1.The yellow pathology of the visible a small amount of point-like of Posterior pole at the bottom of eyes can be found out, be the symptom of abnormal metabolism thing deposition, have no other pathologies.Conclusion: glass-film wart at the bottom of eyes.
Machin (being numbered 1) the fundus fluorescein angiography figure suffering from glass-film wart is shown in Fig. 2.Can find out the visible a small amount of punctate fluorescence of Posterior pole at the bottom of eyes, right eye is comparatively obvious, has no other abnormal fluorescences.Conclusion: suffer from glass-film wart at the bottom of eyes.
Three, modeling method
1. the raising method of blank group: feed with the above-mentioned basal feed prepared, feed 3 every day, each feeding volume is 75-100 gram.
2. the raising method of experimental group: feed with the above-mentioned high lipid food prepared, feed 3 every day, each feeding volume is 75-100 gram.
3. modeling is observed: feed 60 days, carry out tracing observation by color fundus photograph, fundus fluorescein angiography and optical coherence tomography to non-human primate, and observed frequency each week observes once.When observing retinal pigment epithelium atrophy, obtain stable Dry macular degeneration model; When observe have new vessels to be formed between retinal pigment epithelium and Bruch ' s film time, stable wet MD model can be obtained.
Four, experimental result
1. blank group of situation: blank group 8 machins, feed during 60 days to 130 days, each week carries out tracing observation 1 time to non-human primate.Respectively by color fundus photograph, fundus fluorescein angiography and optical coherence tomography, blank group 8 machins are detected, result shows: 8 machins are substantially the same with situation before test: eyeground Posterior pole or macula area have the symptom that abnormal metabolism thing deposits, have no and obviously increase the weight of symptom, there is not PE atrophy or CNV symptom, namely all do not occur macular degeneration pathology yet.
2. experimental group situation
The present invention through 130 days nursing and observe detect, 1 example is only had not occur ARM, the success rate of modeling is 90%, and moist or dryness two type macular degeneration model can be obtained, wherein have 20% for wet MD model, have 70% for Dry macular degeneration model, the model obtained is very stable, there is not spontaneous recovery phenomenon, in test, the compliance of machin is good, need not perform the operation or put to death animal to check, and modeling cost is very low, for the pathogenesis of research macular degeneration model, the screening of medicine and pharmacodynamic evaluation provide desirable animal model.Concrete condition refers to table 1.
Table 1 experimental group macular degeneration model case table
| Numbering | Age (year) | Make a definite diagnosis the time (my god) | Types of models |
| 1 | 15 | 74 | Dryness |
| 2 | 16 | 95 | Moist |
| 3 | 11 | 60 | Dryness |
| 4 | 17 | 102 | Dryness |
| 5 | 13 | 109 | Dryness |
| 6 | 11 | 130 | Nothing |
| 7 | 10 | 81 | Dryness |
| 8 | 15 | 95 | Dryness |
| 9 | 18 | 67 | Dryness |
| 10 | 14 | 81 | Moist |
Below for the present invention induces successful two type model case:
(1) wet MD model (being numbered 2 machins) situation
See Fig. 3.The color fundus photograph lower-glass body cavity of eyes is clear, has no vitreum propagation; Clear depending on disk boundary, color is light red; Central fovea of macula reflexed light ring disappears, the choroidal atrophy district of all visible 1.5PD size of eyes macular area, and the yellow-white that central authorities of right eye atrophy district are also shown in a 1/4PD size oozes out stove; Blood vessel traveling has no tortuous, and retina is calm, have no retinal depigmentation element, hemorrhage, the situation such as to ooze out.
See Fig. 4.The fundus fluorescein angiography inspection of eyes, retinal circulation time is normal, depending on nipple fluorescence sharpness of border, no abnormality seen height fluorescence; An all visible 1/2PD size low Poison district of eyes macular area central authorities, all the other Posterior pole no abnormality seen fluorescence, blood vessel has no obstruction, covers fluorescence and fluorescence leakage, and background fluorescence is normal, has no fluorescence leakage.
See Fig. 5.The optical coherence tomography of eyes, imaging clearly, visible central fovea of macula shoals, and each layer of retina is well arranged, and retinal thickness is in normal range (NR), and thickness and retinal nerve fiber layer is normal, and Bruch ' s film is still complete; Choroid of right eye is in the visible cystic dilatation of macular area, and all the other blood vessels are without expansion; Left eye macular area swells as seen between RPE layer and choroid, and acoustic image is comparatively strong, is new vessels.
Result shows: wet MD pathology, appears in left eye macular area CNV.
(2) Dry macular degeneration model (being numbered 1 machin) situation
See Fig. 6.Left eye color fundus photograph lower-glass body cavity is clear, has no vitreum propagation; Clear depending on disk boundary, color is light red; Central fovea of macula reflexed light ring is clear, and blood vessel traveling has no tortuous, and retina is calm, visible eyeground more point-like yellow-white pathology, the situation such as have no retinal hemorrhage, ooze out.
See Fig. 7.Left eye fundus fluorescein angiography checks, retinal circulation time is normal, depending on nipple fluorescence sharpness of border, and no abnormality seen height fluorescence; Macular area and Posterior pole visible more amount window sample fluorescence, corresponding with eye-ground photography point-like yellow-white pathology, all the other no abnormality seen fluorescence, blood vessel has no obstruction, covers fluorescence and fluorescence leakage, and background fluorescence is normal, has no fluorescence leakage.
See Fig. 8.Left eye optical coherence tomography, imaging clearly, visible central fovea of macula exists, and each layer of retina is well arranged, and retinal thickness is in normal range (NR), and thickness and retinal nerve fiber layer is normal, and Bruch ' s film is complete smooth; Finding choroid is smooth, and blood vessel is without expansion.
Result shows: Dry macular degeneration pathology, appears in left eye eyeground partial pigment epithelial lesions.
Claims (7)
1. the method for one kind high fat induction primate macular degeneration model, it is characterized in that, the method will suffer from the non-human primate of glass-film verrucosis change, feed with high lipid food, feed 3 every day, each feeding volume is 75-100 gram, feeds 60-110 days, can obtain stable macular degeneration model.
2. high fat induces the method for primate macular degeneration model according to claim 1, it is characterized in that: described high lipid food comprises the raw material of following weight part ratio: basal feed 73 parts, lard 26 parts, vegetable oil 24 parts, 2 parts, egg white, sucrose 2 parts.
3. high fat induces the method for primate macular degeneration model according to claim 2, it is characterized in that: described basal feed comprises the raw material of following percentage by weight: 570 parts, rice, 80 parts, flour, dregs of beans 150 parts, soybean 45 parts, FSPC 40 parts, fish meal 20 parts, chicken meal 50 parts, 8 parts, soya-bean oil, calcium monohydrogen phosphate 12 parts, Choline Chloride 1.5 parts, Paris white 3.6 parts, calcium pantothenate 0.15 part, salt 3.7 parts, vitamin C 0.2 part, vitamin E 0.1 part.
4. the method for high fat induction primate macular degeneration model according to claim 1, is characterized in that: described in suffer from glass-film verrucosis and become eyeground Posterior pole or macula area has the symptom of abnormal metabolism thing deposition through color fundus photograph diagnosis.
5. high fat induces the method for primate macular degeneration model according to claim 1, it is characterized in that: described non-human primate is person in middle and old age's non-human primate.
6. the method for high fat induction primate macular degeneration model according to claim 1, is characterized in that: described person in middle and old age's non-human primate age >=10 years old.
7., according to the method for described high fat induction primate macular degeneration model arbitrary in claim 1-6, it is characterized in that: described non-human primate is machin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510364789.3A CN104982379B (en) | 2015-06-26 | 2015-06-26 | A kind of method that high fat induces primate macular degeneration model |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510364789.3A CN104982379B (en) | 2015-06-26 | 2015-06-26 | A kind of method that high fat induces primate macular degeneration model |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104982379A true CN104982379A (en) | 2015-10-21 |
| CN104982379B CN104982379B (en) | 2017-10-03 |
Family
ID=54294398
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510364789.3A Expired - Fee Related CN104982379B (en) | 2015-06-26 | 2015-06-26 | A kind of method that high fat induces primate macular degeneration model |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104982379B (en) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107348173A (en) * | 2017-08-31 | 2017-11-17 | 中国医学科学院医学实验动物研究所 | A kind of marmoset feed and its preparation technology |
| CN107787912A (en) * | 2017-10-20 | 2018-03-13 | 广东省生物资源应用研究所 | A kind of abductive approach of Local Electroretinogram primate model |
| CN111869625A (en) * | 2020-09-18 | 2020-11-03 | 四川大学华西医院 | High-fat high-sugar diet-induced dry age-related macular degeneration pigment rabbit model |
| CN111990339A (en) * | 2020-09-18 | 2020-11-27 | 四川大学华西医院 | High-sugar diet-induced early dry age-related macular degeneration pigment rabbit model |
| CN112219788A (en) * | 2020-09-29 | 2021-01-15 | 四川大学华西医院 | Construction method and application of high-fat diet-induced anterior ischemic optic neuropathy chromogen rabbit model |
| CN113615641A (en) * | 2021-08-23 | 2021-11-09 | 浙江大学 | Method for artificially feeding newborn marmosets |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101279356B1 (en) * | 2011-09-06 | 2013-07-04 | 한림대학교 산학협력단 | Osteoarthritis model animal |
| CN103314925A (en) * | 2013-06-21 | 2013-09-25 | 四川大学华西医院 | Method for preparing rhesus monkey type 2 diabetic model |
| CN103416608A (en) * | 2012-12-28 | 2013-12-04 | 广西南宁灵康赛诺科生物科技有限公司 | Experimental-type high-fat primate feed and preparation method thereof |
-
2015
- 2015-06-26 CN CN201510364789.3A patent/CN104982379B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101279356B1 (en) * | 2011-09-06 | 2013-07-04 | 한림대학교 산학협력단 | Osteoarthritis model animal |
| CN103416608A (en) * | 2012-12-28 | 2013-12-04 | 广西南宁灵康赛诺科生物科技有限公司 | Experimental-type high-fat primate feed and preparation method thereof |
| CN103314925A (en) * | 2013-06-21 | 2013-09-25 | 四川大学华西医院 | Method for preparing rhesus monkey type 2 diabetic model |
Non-Patent Citations (1)
| Title |
|---|
| 王宇寰: "高脂饮食诱导的食蟹猴代谢综合症模型的建立及其特征的鉴定", 《2013第二届糖尿病大会论文集》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107348173A (en) * | 2017-08-31 | 2017-11-17 | 中国医学科学院医学实验动物研究所 | A kind of marmoset feed and its preparation technology |
| CN107787912A (en) * | 2017-10-20 | 2018-03-13 | 广东省生物资源应用研究所 | A kind of abductive approach of Local Electroretinogram primate model |
| CN107787912B (en) * | 2017-10-20 | 2023-04-11 | 广东省科学院动物研究所 | Induction method of primate model with dry age-related macular degeneration |
| CN111869625A (en) * | 2020-09-18 | 2020-11-03 | 四川大学华西医院 | High-fat high-sugar diet-induced dry age-related macular degeneration pigment rabbit model |
| CN111990339A (en) * | 2020-09-18 | 2020-11-27 | 四川大学华西医院 | High-sugar diet-induced early dry age-related macular degeneration pigment rabbit model |
| CN112219788A (en) * | 2020-09-29 | 2021-01-15 | 四川大学华西医院 | Construction method and application of high-fat diet-induced anterior ischemic optic neuropathy chromogen rabbit model |
| CN113615641A (en) * | 2021-08-23 | 2021-11-09 | 浙江大学 | Method for artificially feeding newborn marmosets |
| CN113615641B (en) * | 2021-08-23 | 2022-10-14 | 浙江大学 | Method for artificially feeding newborn marmosets |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104982379B (en) | 2017-10-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN104982379B (en) | A kind of method that high fat induces primate macular degeneration model | |
| Lee et al. | In vivo foveal development using optical coherence tomography | |
| Howlett et al. | Emmetropization and schematic eye models in developing pigmented guinea pigs | |
| Wilson et al. | Report of a fatal case of keratomalacia in an infant, with postmortem examination | |
| Squarzoni et al. | Ultrasonographic aspects and biometry of Striped owl’s eyes (Rhinoptynx clamator) | |
| Duguid | Chronic endophthalmitis due to Toxocara | |
| CN103416608B (en) | Experimental-type high-fat primate feed and preparation method thereof | |
| Kuhn et al. | Normal ocular parameters and characterization of ophthalmic lesions in a group of captive bald eagles (Haliaeetus leucocephalus) | |
| CN106535919A (en) | Brain function improving agent, and prophylactic or therapeutic agent for cognitive dysfunction | |
| Ahn et al. | Cataract formation associated with ocular toxocariasis | |
| CN107787912A (en) | A kind of abductive approach of Local Electroretinogram primate model | |
| Yamashita et al. | Differences of body height, axial length, and refractive error at different ages in Kumejima study | |
| CN105997973A (en) | Therapeutic or prophylactic agent for corneal epithelium disorders and/or conjunctival epithelium disorders | |
| CN103732223A (en) | Medical food for cognitive decline | |
| Falk et al. | Developmental and reproductive toxicological evaluation of arachidonic acid (ARA)-Rich oil and docosahexaenoic acid (DHA)-Rich oil | |
| CN109303784A (en) | The construction method of urarthritis animal model | |
| Presby et al. | Normative ocular data for juvenile and adult Japanese quail (Coturnix japonica) | |
| CN113826582A (en) | Modeling and evaluation method of acute gouty arthritis symptom combined rat model | |
| Hetler | The Development of Xerophthalmia and the Keratinization of Epithelial Tissue on Withdrawal of Vitamin A from the Diet of the Monkey (Macacus Rhesus) Guinea PigRabbitand Adult Albino Rat: Six Text Figures and Four Plates (Twenty-Two Figures) | |
| Satran et al. | Neurofibromatosis with congenital glaucoma and buphthalmos in a newborn | |
| CN105920605A (en) | Application of anti-inositol metabolism medicament to establishment of mouse model with NTDs | |
| Liang et al. | Ophthalmic examination of the captive western lowland gorilla (Gorilla gorilla gorilla) | |
| Woodhouse et al. | Intraocular pressure in southern rockhopper (Eudyptes chrysocome) and macaroni penguins (Eudyptes chrysolophus): evaluation of influencing factors | |
| Oshima et al. | Examination of postmortem retinal folds: A non-invasive study | |
| Yasuda et al. | Embryotoxic effects of feeding bracken fern (Pteridium aquilinum) to pregnant mice |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20171003 |