Molecular Assessment of Epiretinal Membrane: Activated Microglia, Oxidative Stress and Inflammation.

Sushma Vishwakarma,Inderjeet Kaur,Gregory Hendricks,Michael R Volkert,Rajeev Reddy Pappuru,Rishikesh Kumar Gupta,Keith Reddig,Jay Chhablani,Hemant Khanna,Mudit Tyagi,Saumya Jakati

doi:10.3390/antiox9080654

Abstract

Fibrocellular membrane or epiretinal membrane (ERM) forms on the surface of the inner limiting membrane (ILM) in the inner retina and alters the structure and function of the retina. ERM formation is frequently observed in ocular inflammatory conditions, such as proliferative diabetic retinopathy (PDR) and retinal detachment (RD). Although peeling of the ERM is used as a surgical intervention, it can inadvertently distort the retina. Our goal is to design alternative strategies to tackle ERMs. As a first step, we sought to determine the composition of the ERMs by identifying the constituent cell-types and gene expression signature in patient samples. Using ultrastructural microscopy and immunofluorescence analyses, we found activated microglia, astrocytes, and Müller glia in the ERMs from PDR and RD patients. Moreover, oxidative stress and inflammation associated gene expression was significantly higher in the RD and PDR membranes as compared to the macular hole samples, which are not associated with inflammation. We specifically detected differential expression of hypoxia inducible factor 1-α (HIF1-α), proinflammatory cytokines, and Notch, Wnt, and ERK signaling pathway-associated genes in the RD and PDR samples. Taken together, our results provide new information to potentially develop methods to tackle ERM formation.

Highlights

The retina is a multilayered light-sensing neural tissue located at the back of the eye [1]
The cellularity varied among specimens; it was lower in macular hole samples as compared to proliferative diabetic retinopathy (PDR)
We have shown the involvement of microglial cells, inflammation and oxidative stress in fibrocellular membranes (ERM/inner limiting membrane (ILM)) of different pathological conditions

Summary

Introduction

The retina is a multilayered light-sensing neural tissue located at the back of the eye [1]. The ganglion cell layer is composed of Muller glia, whose foot processes are embedded into a thin transparent layer in the basal lamina of the inner retina called the inner limiting membrane (ILM). Ischemic conditions lead to accumulation/activation of the transcription factor, hypoxia-inducible factor (HIF-1α), which causes secretion of vasoactive cytokines vascular leakage and macular edema [7]. Growth factors such as hepatocyte growth factor (HGF), heparin-binding epidermal growth factor (HB-EGF), and epidermal growth factor (EGF) others and other inflammatory molecules released due to any retinal insults induce the migration of retinal cells like RPE to the vitreous to proliferate and induce the retinal membrane formation.

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