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An Ex Vivo Tissue Culture Model for Fibrovascular Complications in Proliferative Diabetic Retinopathy
Published on: January 25, 2019
miR-92a and integrin expression in fibrovascular membranes in proliferative diabetic retinopathy
Qianyi Luo1, Amir R Hajrasouliha1, Ashay D Bhatwadekar1
1Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University, Indianapolis, IN, United States.
Abstract:
Diabetic retinopathy (DR) is a leading cause of vision impairment. The proliferative form of DR (PDR) involves fibrovascular membrane (FVM) formation at the vitreoretinal interface. MicroRNAs (miRNAs) are a class of non-coding RNA molecules that play an important role in gene regulation; a single miRNA could regulate multiple genes. We previously reported that miR-92a, a suppressor of integrins α5 and αv, was downregulated in DR. Considering the integrin's role in FVM pathology and the potential involvement of miR-92a in DR, we asked a question whether miR-92a could play a critical role in FVM pathology. We collected the FVM and epiretinal membranes of individuals with PDR and macular pucker (control) undergoing pars plana vitrectomy. The frozen sections of membranes were stained for α5 and αvβ3 integrins. The miR-92a levels were assessed using real-time quantitative PCR. The FVMs of individuals with PDR stained brighter for integrin subunits α5 and αvβ3 compared to the epiretinal membranes of subjects with macular pucker. miR-92a levels were decreased in FVM subjects. In conclusion, our studies demonstrate that miR-92a decrease is associated with an increase in integrins α5 and αvβ3, thus contributing to the inflammatory milieu in PDR.
Insights
Decreased miR-92a levels in diabetic retinopathy (DR) are linked to increased integrins, contributing to fibrovascular membrane (FVM) formation. This finding highlights miR-92a
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Diabetic retinopathy (DR) is a major cause of vision loss.
- Proliferative DR (PDR) involves fibrovascular membrane (FVM) formation.
- MicroRNAs (miRNAs) regulate gene expression and are implicated in disease.
Purpose of the Study:
- To investigate the role of miR-92a in the pathogenesis of FVM in PDR.
- To determine the relationship between miR-92a levels and integrin expression in FVM.
Main Methods:
- Collected FVM from PDR patients and epiretinal membranes from controls.
- Performed immunohistochemical staining for α5 and αvβ3 integrins.
- Quantified miR-92a levels using real-time quantitative PCR.
Main Results:
- FVM samples showed significantly higher expression of α5 and αvβ3 integrins compared to controls.
- miR-92a levels were significantly decreased in FVM samples from PDR patients.
- A negative correlation was observed between miR-92a levels and integrin expression.
Conclusions:
- Reduced miR-92a levels are associated with increased integrin expression in PDR.
- This upregulation of integrins may contribute to the inflammatory FVM formation in PDR.
- miR-92a represents a potential therapeutic target for managing PDR.

