MiR-29 related deposition of extracellular matrix in Fuchs endothelial corneal dystrophy

Abstract

Purpose : Previous studies demonstrate reduced expression of the microRNA (miR)-29 family with concomitant overexpression of extracellular matrix-related target genes in the corneal endothelium of FECD patients. The present study aimed to analyze the miR-29 related deposition of ECM in FECD in more detail.

Methods : The differential expression of miR-29 and its target genes in corneal endothelial specimens from FECD and normal corneas was analyzed by Stem-loop RT-qPCR and RNA sequencing. The differential expression of individual miR-29 target genes was located by immunofluorescence staining in corneal endothelial flatmounts. MiR-29 knockdown in a corneal endothelial cell line (HCEC-12) was used to recapitulate FECD-related ECM expression in vitro.

Results : Reduced miR-29 expression was confirmed in CEC samples from FECD (n = 14) compared to normal (n = 7) corneas. RNA sequencing analysis in the same samples showed significant overexpression of a wide range of miR-29-related target genes including a variety of collagens, laminins, fibrillin, and elastin. Immunofluorescence of individual target genes in FECD endothelial flatmounts revealed central accumulation of corresponding proteins covering areas with significant reduction of corneal endothelial cell density. MiR-29 knock-down induced overexpression of ECM-related target-genes including COL1A1 and COL4A1.

Conclusions : The present study provides further evidence for a role of miR-29-related deposition of ECM and in the pathogenesis of FECD. Further studies will investigate the potential of miR-29 substitution to serve as a therapeutic approach in FECD.

This is a 2020 ARVO Annual Meeting abstract.