Molecular Assessment of Epiretinal Membrane: Activated Microglia, Oxidative Stress and Inflammation
Sushma Vishwakarma1,2, Rishikesh Kumar Gupta1, Saumya Jakati3
1Prof Brien Holden Eye Research Centre, LV Prasad Eye Institute, Hyderabad 500034, India.
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.
Insights
Epiretinal membranes (ERMs) involve activated glial cells and show higher inflammation gene expression in conditions like proliferative diabetic retinopathy. Understanding ERM composition may lead to new therapeutic strategies.
Area of Science:
- Ophthalmology
- Retinal Biology
- Cellular and Molecular Medicine
Background:
- Epiretinal membranes (ERMs) form on the inner limiting membrane (ILM), altering retinal structure and function.
- ERM formation is common in inflammatory eye conditions such as proliferative diabetic retinopathy (PDR) and retinal detachment (RD).
- Current surgical ERM peeling can cause retinal distortion, necessitating alternative treatment strategies.
Purpose of the Study:
- To investigate the cellular composition and gene expression profile of ERMs from patients with PDR and RD.
- To identify key molecular pathways involved in ERM formation in inflammatory ocular conditions.
Main Methods:
- Ultrastructural microscopy and immunofluorescence analyses were performed on patient-derived ERM samples.
- Gene expression profiling focused on identifying signatures related to oxidative stress, inflammation, and specific signaling pathways.
Main Results:
- Activated microglia, astrocytes, and Müller glia were identified within ERMs from PDR and RD patients.
- ERMs from RD and PDR samples exhibited significantly higher expression of inflammation and oxidative stress-related genes compared to macular hole samples.
- Differential gene expression of hypoxia-inducible factor 1-α (HIF1-α), proinflammatory cytokines, and Notch, Wnt, and ERK signaling pathways was observed in RD and PDR ERMs.
Conclusions:
- The cellular makeup of ERMs includes activated glial cells, particularly in inflammatory conditions.
- Specific gene expression patterns, including inflammatory and signaling pathway markers, are associated with ERM formation in PDR and RD.
- These findings offer insights for developing novel therapeutic approaches to prevent or treat ERM formation.
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