CN-122005802-A - Application of NCOA3 polyQ domain as target in preparation of drugs for relieving eye abnormal proliferation diseases

CN122005802ACN 122005802 ACN122005802 ACN 122005802ACN-122005802-A

Abstract

The application provides application of NCOA3 polyQ structural domain in preparation of drugs for relieving ocular vascular abnormal proliferation diseases, relates to the technical field of biomedicine, and aims at solving the problems that an ocular pathological angiogenesis mechanism is complex and a safe and effective targeted intervention means is lacking in the prior art, by constructing a mouse cornea micro-pocket pathological angiogenesis model, the fact that Ncoa polyQ structural domain deletion can obviously inhibit cornea neovascularization is proved to be compared with a WT mouse, CD31 positive signals of cornea tissue of the Ncoa3 wt/△Q mouse are reduced, cornea neovascularization is minimum in the Ncoa3 △Q/△Q mouse, CD31 positive areas are also minimum, and meanwhile, mRNA expression of vascular marker genes Pecam1 and Cdh5 is reduced in a trend through cornea tissue qPCR detection and is further down-regulated in the Ncoa3 △Q/△Q mouse. Based on the above, the application provides an intervention strategy aiming at the NCOA3 polyQ domain for preparing a medicine for relieving the ocular vascular abnormal proliferative diseases, and provides a new treatment strategy and a potential target point for the ophthalmic related diseases.

Inventors

JIANG YIJING
MAO RENFANG
WANG ZIBO
FAN YIHUI

Assignees

南通大学

Dates

Publication Date: 20260512
Application Date: 20260211

Claims (7)

Application of NCOA3 polyQ domain as target in preparing medicament for relieving eye abnormal proliferation diseases.
2. The use of the NCOA3 polyQ domain as target according to claim 1 for preparing a medicament for alleviating eye abnormal proliferative diseases, wherein the medicament is used for inhibiting the function of the NCOA3 polyQ domain and blocking the angiogenesis-related effect mediated by the NCOA3 polyQ domain.
3. The use of NCOA3 polyQ domain as target according to claim 2 for preparing a medicament for alleviating eye dysplasia diseases, wherein the eye dysplasia diseases comprise diseases related to pathological cornea production.
4. The use of NCOA3 polyQ domain as target spot in preparing medicament for relieving eye abnormal proliferation diseases, wherein the eye abnormal proliferation diseases comprise abnormal vascular proliferation and leakage driven by ischemia and anoxia frequently accompanied by diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, etc. according to claim 3.
5. A drug for relieving ocular dysplasia is characterized in that the drug is used for inhibiting the function of NCOA3 polyQ domain and blocking the angiogenesis related effect mediated by NCOA3 polyQ domain.
6. The drug for relieving ocular dysplasia of claim 5, wherein the drug comprises at least one of nucleic acid intervention preparation, gene editing intervention system and small molecule compound for NCOA3 polyQ domain.
7. The drug for relieving ocular dysproliferation according to claim 6, wherein the drug further comprises other pharmaceutically acceptable auxiliary agents.

Description

Application of NCOA3 polyQ domain as target in preparation of drugs for relieving eye abnormal proliferation diseases Technical Field The application relates to the technical field of biomedicine, in particular to application of NCOA3 polyQ domain as a target in preparation of a medicament for relieving eye abnormal proliferation diseases. Background The abnormal hyperplasia of ocular blood vessel is a kind of disease which takes abnormal angiogenesis, dilatation or leakage of ocular or ocular surface tissue as main pathological characteristics and can involve cornea, conjunctiva, iris, retina, choroid and other parts. Under normal conditions, the cornea is in a 'avascular' state to maintain transparent and refractive functions, and when factors such as infection, inflammation, trauma, hypoxia, immune response and the like destroy the steady state of the cornea microenvironment, limbal blood vessels can invade the center of the cornea to form new blood vessels, so that corneal edema, turbidity, lipid deposition and scar formation are caused, vision is reduced and even blindness is caused, and the success rate of cornea transplantation is obviously reduced. In addition to cornea, ocular fundus pathologic angiogenesis is also an important cause of irreversible visual function impairment, such as abnormal vascular proliferation and leakage often accompanied by ischemia and hypoxia driving, such as diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion, and the like, and wet age-related macular degeneration is characterized by choroidal neovascularization, is liable to leak and bleed and damage macular structure, resulting in rapid decrease of central vision. The diseases are mostly characterized by hidden, progressive and recurrent, once bleeding, exudation or fibrotic scars appear, long-term and even permanent vision disorder is often caused, so that inhibiting pathological angiogenesis is an important direction of ophthalmic treatment and blindness prevention. Pathological angiogenesis is driven by multiple factors and multiple links, and relates to vascular endothelial cell proliferation and migration, basement membrane degradation, pericyte coverage abnormality, inflammatory cell infiltration, extracellular matrix remodeling and the like. VEGF/VEGFR pathway plays a key role in various ocular neovascular diseases, anti-VEGF drugs have been widely used in wet age-related macular degeneration, diabetic macular edema and the like, but have the problems of difference and tolerance of curative effect, risk of infection/hemorrhage/elevated intraocular pressure and compliance caused by repeated intravitreal injection, and the long-term inhibition of VEGF possibly affects normal vascular homeostasis and neuroprotection, and the defects of delivery, continuous effect, recurrence control and the like in ocular surface lesions such as cornea neovascular and the like. Besides VEGF, inflammatory mediators such as TNF-alpha, IL-1 beta, IL-6 and the like and signals such as Notch, ang/Tie, HIF and the like are involved in pathogenesis, long-term stable curative effect is often difficult to obtain by single-channel intervention, and a more upstream regulation target point needs to be searched. Disclosure of Invention The application aims to solve the problems of insufficient ocular pathologic angiogenesis targets and lack of treatment means in the prior art. In order to solve the technical problems, the application provides the following technical scheme: The NCOA3 polyQ domain is used as a target spot in the preparation of medicines for relieving eye abnormal proliferation diseases. Preferably, the medicament is for inhibiting the function of the NCOA3 polyQ domain and blocking the angiogenesis-related effects mediated by the NCOA3 polyQ domain. Preferably, the ocular dysplastic disease comprises a disease associated with pathological generation of the cornea. Preferably, the ocular abnormal proliferative diseases comprise abnormal vascular proliferation and leakage which are frequently accompanied by ischemia and hypoxia driving, such as diabetic retinopathy, retinopathy of prematurity, retinal vein occlusion and the like. The application also provides an agent for alleviating ocular dysplasia, which is used for inhibiting the function of the NCOA3 polyQ domain and blocking the angiogenesis-related effect mediated by the NCOA3 polyQ domain. Preferably, the medicament comprises at least one of a nucleic acid intervention agent, a gene editing intervention system and a small molecule compound for the NCOA3 polyQ domain. Preferably, the medicament further comprises other auxiliary agents which are acceptable in medicine. Compared with the prior art, the application has the following beneficial effects: The application discloses the direct association of the NCOA3 polyQ domain and the pathological angiogenesis process in the ocular vascular abnormal hyperplasia disease for the first time, and the internal f