CN107898793B - Method for inhibiting myopia and application of prepared medicine - Google Patents
Method for inhibiting myopia and application of prepared medicine Download PDFInfo
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- CN107898793B CN107898793B CN201711246224.0A CN201711246224A CN107898793B CN 107898793 B CN107898793 B CN 107898793B CN 201711246224 A CN201711246224 A CN 201711246224A CN 107898793 B CN107898793 B CN 107898793B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to a method for inhibiting myopia and application of a prepared medicament, which inhibits myopia by inhibiting phosphorylation of an intraocular eukaryotic translation initiation factor 2 alpha subunit (eIF 2 alpha), and inhibits myopia by inhibiting activity of intraocular PKR-like endoplasmic reticulum kinase so as to inhibit phosphorylation of eIF2 alpha.
Description
Technical Field
The invention relates to a method for inhibiting myopia and application of a prepared medicament.
Background
Myopia in humans is commonly characterized by hyperelongation of the axis of the eye, which is a refractive error caused by hyperelongation of the axis of the eye in order to obtain clear retinal images. Highly myopic people with diopters above-6.00D are more likely to develop progressive retinal atrophy, as well as atrophy of the retinal pigment epithelium and choroid. This allows the retina to acquire a reduced number of molecules that maintain its basic function. In other retinal and macular diseases, this condition causes a series of oxidative stress injuries.
eIF2 is eukaryotic translation initiation factor 2. Both hypoxia and oxidative stress have been found to activate PERK, an eIF2 α kinase, inducing eIF2 α phosphorylation, ultimately inhibiting protein translation processes.
Disclosure of Invention
In order to solve the defects of the prior art, the invention discovers that the eIF2 pathway of the scleral fibroblast is activated during the formation of myopia, and suggests that the eIF2 pathway may play an important role in the development of the myopia. Therefore, the invention provides a method for inhibiting myopia and application of a prepared medicament, and finds a method for inhibiting myopia by inhibiting phosphorylation of an intraocular eukaryotic translation initiation factor 2 alpha subunit (eIF 2 alpha).
The technical solution adopted by the invention is as follows: a method of inhibiting myopia by inhibiting phosphorylation of the intraocular eukaryotic translation initiation factor 2 alpha subunit (eIF 2 alpha).
The method comprises the following steps: myopia is inhibited by inhibiting intraocular PKR-like endoplasmic reticulum kinase activity, thereby inhibiting eIF2 alpha phosphorylation.
Use of an inhibitor of PKR-like endoplasmic reticulum kinase (PERK) in the manufacture of a medicament for the inhibition of myopia.
The inhibitor of PKR-like endoplasmic reticulum kinase (PERK) is GSK 2606414.
Application of GSK2606414 in preparing medicine for inhibiting phosphorylation of intraocular eukaryotic translation initiation factor 2 alpha subunit (eIF 2 alpha).
The invention has the beneficial effects that: the invention provides a method for inhibiting myopia and application of a prepared medicament, which can inhibit myopia by inhibiting phosphorylation of an intraocular eukaryotic translation initiation factor 2 alpha subunit (eIF 2 alpha), and inhibit myopia by inhibiting activity of an intraocular PKR-like endoplasmic reticulum kinase so as to inhibit phosphorylation of eIF2 alpha.
Drawings
FIG. 1 is a graph of the effect of the amount of myopia induction in monocular perception deprived mice two weeks after intraperitoneal injection of different doses of GSK 2606414.
In the figure, "interval difference of recovery" refers to the difference between the diopter of the deprived eye and the diopter of the contralateral eye, and reflects the myopia induction amount of the monocular form factor deprivation; comparison between GSK2606414 (i.e. GSK) injected solvent group and dosing group two-way anova with repeated measurements: "-" indicates P < 0.05.
Detailed Description
The experimental animals adopted in the experiment are all 3-week-old C57BL/6J mice. The eye patch method was used as a monocular Form Deprivation (FD) myopia model.
In the administration experiment, PERK inhibitor GSK2606414 is injected into the abdominal cavity of a form-deprived mouse, so that the phosphorylation of the intraocular eIF2 alpha is inhibited. Animals in GSK2606414 injection experiments were randomized into 3 groups: form deprivation + solvent control group (FD +1% dimethyl sulfoxide (DMSO)), form deprivation + low dose drug group (FD + GSK 100. mu.g/Kg body weight), form deprivation + high dose drug group (FD + GSK 330. mu.g/Kg body weight). The administration was performed by intraperitoneal injection at 9 am every day for 2 weeks. Diopters were measured with an infrared eccentric optometry (EIR) before the experiment, at 2 weeks after dosing.
Comparing the diopter before and after the experiment, the form-deprived eyes of the administration group are found, the refractive myopia degree is smaller than that of the form-deprived solvent group, and the dosage dependence is shown, and the statistical significance is realized compared with that of the solvent control group. Therefore, the effect of inhibiting eIF2 alpha phosphorylation by intraperitoneal injection of PERK inhibitor GSK2606414 can inhibit the formation of form-deprivation myopia of mice.
As can be seen from fig. 1, after 2 weeks of the experiment, the amount of myopia formation was significantly reduced in the form-deprivation injected GSK2606414 compared to the form-deprivation injected solvent group, indicating that the PERK inhibitor GSK2606414 can inhibit the progression of form-deprivation myopia.
The experiment proves that eIF2 alpha participates in myopia, and inhibition of eIF2 alpha phosphorylation activity by PERK inhibitor GSK2606414 can obviously play a role in myopia retardation.
The above description is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above embodiments, and all technical solutions belonging to the idea of the present invention belong to the protection scope of the present invention. It should be noted that modifications and embellishments within the scope of the invention may occur to those skilled in the art without departing from the principle of the invention, and are considered to be within the scope of the invention.
Claims (1)
1. Use of an inhibitor of PKR-like endoplasmic reticulum kinase (PERK) for the manufacture of a medicament for inhibiting myopia, wherein the inhibitor of PKR-like endoplasmic reticulum kinase (PERK) is GSK 2606414.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711246224.0A CN107898793B (en) | 2017-12-01 | 2017-12-01 | Method for inhibiting myopia and application of prepared medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711246224.0A CN107898793B (en) | 2017-12-01 | 2017-12-01 | Method for inhibiting myopia and application of prepared medicine |
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| Publication Number | Publication Date |
|---|---|
| CN107898793A CN107898793A (en) | 2018-04-13 |
| CN107898793B true CN107898793B (en) | 2019-12-24 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201711246224.0A Active CN107898793B (en) | 2017-12-01 | 2017-12-01 | Method for inhibiting myopia and application of prepared medicine |
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Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116761595A (en) * | 2020-12-11 | 2023-09-15 | 坪田实验室股份有限公司 | Eye drops for inhibiting myopia progression of children and screening method of myopia progression inhibitor for children |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102078614A (en) * | 2010-12-27 | 2011-06-01 | 温州医学院眼视光研究院 | Method for inhibiting shortsightedness and application of adenylate cyclase inhibitor as medicament for inhibiting shortsightedness |
| WO2015056180A1 (en) * | 2013-10-15 | 2015-04-23 | Glaxosmithkline Intellectual Property (No.2) Limited | Indoline derivatives as inhibitors of perk |
| WO2017046737A1 (en) * | 2015-09-15 | 2017-03-23 | Glaxosmithkline Intellectual Property (No.2) Limited | 1-phenylpyrrolidin-2-one derivatives as perk inhibitors |
| CN106963769A (en) * | 2017-03-03 | 2017-07-21 | 深圳大学 | The pharmaceutical composition and its application of inhibitor containing PI3K and PERK inhibitor |
| CN107320725A (en) * | 2017-06-29 | 2017-11-07 | 温州医科大学 | A kind of method for suppressing myopia and the application for preparing medicine |
-
2017
- 2017-12-01 CN CN201711246224.0A patent/CN107898793B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102078614A (en) * | 2010-12-27 | 2011-06-01 | 温州医学院眼视光研究院 | Method for inhibiting shortsightedness and application of adenylate cyclase inhibitor as medicament for inhibiting shortsightedness |
| WO2015056180A1 (en) * | 2013-10-15 | 2015-04-23 | Glaxosmithkline Intellectual Property (No.2) Limited | Indoline derivatives as inhibitors of perk |
| WO2017046737A1 (en) * | 2015-09-15 | 2017-03-23 | Glaxosmithkline Intellectual Property (No.2) Limited | 1-phenylpyrrolidin-2-one derivatives as perk inhibitors |
| CN106963769A (en) * | 2017-03-03 | 2017-07-21 | 深圳大学 | The pharmaceutical composition and its application of inhibitor containing PI3K and PERK inhibitor |
| CN107320725A (en) * | 2017-06-29 | 2017-11-07 | 温州医科大学 | A kind of method for suppressing myopia and the application for preparing medicine |
Non-Patent Citations (2)
| Title |
|---|
| Discovery of 7-methyl-5-(1-{[3-(trifluoromethyl)phenyl]acety}-2,;Jeffrey M. Axten等;《Journal of Medical Chemistry》;20120724;第 55卷;7193-7207 * |
| UPR activation and the down-regulation of α-crystallin in human high myopia-related cataract lens epithelium;Jing Yang等;《PLOS ONE》;20150909;第10卷(第9期);1-11 * |
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| CN107898793A (en) | 2018-04-13 |
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