Alterations of cell junction protein expression in Fuchs endothelial corneal dystrophy.

Abstract

Purpose : Fuchs endothelial corneal dystrophy (FECD) is characterized by a progressive corneal endothelial dysfunction leading to stromal edema. Cell polarity of tight and adherens junction proteins is necessary for adequate corneal endothelial functionality. The goal of this study was to examine the localisation of cell junction proteins in FECD chirurgical specimens.

Methods : Central Descemet membranes (8 mm diameter) isolated from FECD patients at the time of corneal transplantation (n=20) were fixed in 4% paraformaldehyde. Central Descemet membranes from healthy Eye bank corneas (n=15) were used as controls. The presence of the cell adhesion regulator β-catenin, the adherens junction protein N-cadherin and the tight junction protein ZO-1 was detected using immunofluorescence and immunohistochemistry. Cell diameter was measured using cell analysis software.

Results : A high level of heterogeneity was observed in FECD specimens. (1) Some regions (mostly at the periphery of the specimens) showed small hexagonal cells (mean diameter = 9.3 ± 1.6 µm) and a junctional proteins cytolocalisation similar to the healthy controls. (2) Other regions, with few guttae, presented enlarged cells, with marked pleomorphism and polymegethism (mean diameter = 19.4 ± 10.0 µm). These second regions showed lower levels of N-cadherin and β-catenin expression at the cell borders. ZO-1 protein expression, however, was similar to that of healthy cells. (3) Regions with larger numbers of guttae presented packed, small, polymorphous cells (mean diameter = 7.5 ± 3.1 µm), with a loss of N-Cadherin and β-catenin expression at the cell membrane, a high expression of N-cadherin around guttae, and intra-cellular aggregates of β-catenin at the peri-nuclear area in 100% of the cells. ZO-1 was still normally located at the membrane in all guttae-rich FECD specimens.

Conclusions : This study demonstrates that, contrary to tight junctions, adherens junctions are altered in FECD, especially in guttae-rich regions of Descemet membranes. Since adherens junction support cell polarity by strengthening the link between cells, their loss will likely have consequences in the adequate distribution of proteins that maintain corneal dehydration.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.