Micro-RNAs in the pathogenesis of epiretinal membrane (ERM) formation

Abstract

Purpose : Epiretinal membrane (ERM) formation involves the migration of Muller glial cells (MGCs) through damaged internal limiting membrane, followed by the transition of MGCs to a myofibroblast-like state, similar to the endothelial to mesenchymal transition (EMT) that occurs oncologically. We hypothesize that microRNAs (miRs) are central to this process. The aim of this study was to identify altered miR expression patterns in ERM tissue samples compared with controls.

Methods : ERM tissue was collected under IRB approval and with informed consent during routine vitrectomy from patients with ERM undergoing membrane peel. Control vitreous was collected from patients undergoing vitrectomy for primary symptomatic idiopathic floaters without ERM. A NanoString nCounter^TM assay was used to quantify (by solution hybridization without amplification) and compare miRs expressed in ERM tissue with control vitreous. Raw counts for each miR were normalized and analyzed using nSolver^TM analysis software to obtain differential expression analysis of 800 miRs.

Results : MiR expression profiles of ERM tissue from 4 eyes were compared with circulating vitreous miRs from 2 control eyes. Twelve miRs were downregulated in ERM tissue compared with control vitreous. Of the 800 miRs assayed, we identified only miR-494-3p, a known positive regulator of EMT, as the only miR expressed at significantly greater levels in ERM tissue compared with control vitreous (p=0.002; CI: 1.23-1.66).

Conclusions : This is the first study to investigate miR profiles of ERM specimens. MiR-494-3p was significantly increased in ERM specimens relative to vitreous controls, suggesting that miR-494-3p could be a potential therapeutic target to inhibit MGC migration and myofibroblast-like transformation associated with the pathophysiology of ERMs.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.