New evidence suggesting that the central endothelium presents features of peripheral endothelium in Fuchs endothelial corneal dystrophy

Abstract

Purpose : Most recent studies about Fuchs endothelial corneal dystrophy (FECD) highlight its complex and heterogeneous genetic background. Yet, the sequence of cellular mechanisms leading to the formation of Descemet excrescences (guttae), endothelial cell (EC) premature death and loss of pumping functions remains poorly understood. Aim: to present new phenotypic characteristics of ECs observed in late onset FECD, opening new perspectives in understanding its pathogenesis.

Methods : Thirty corneal central buttons (8mm in diameter) were collected from FECD patients, and immediately processed for microscopic observation. They were compared with fresh normal whole corneas (body donation to science), and with corneas stored at 31°C in organ culture (OC) (CorneaMax, Eurobio) for various periods of time. Mean donor age was 72 years. We also analysed 6 whole corneas from donors with early stages of FECD. We used en face microscopy of flat mounted corneas. The morphology of ECs and of guttae was studied after staining with alizarin red. The expression of EC markers, of stem cell markers, and of extracellular matrix was studied using immunofluorescence optimized for flat mounted whole corneas. Proliferating and dead cells were also investigated.

Results : Central ECs of FECD specimens and peripheral ECs of fresh corneas shared common features: weaker expression of the usual CE markers (Na/K ATPase, ZO-1, COX IV, Vimentin, NCAM, N-cadherin), expression of stem cells markers (nestin, c-myc, telomerase, CD44), presence of proliferating cells (Ki67), presence of numerous dead cells (ethidium), numerous cells containing pigment, isolated and confluent guttae, thicker Descemet membrane (DM), and localization of collagen I, IV and V. In corneas with early stages of FECD, the peripheral endothelium (collagen I, IV and V) was significantly enlarged. This was also observed in normal corneas after 3 years of OC preservation.

Conclusions : These new features of ECs and DM suggest that central ECs of FECD acquire or retain characteristics of peripheral ECs of healthy corneas, corresponding to less differentiated cells. We therefore suggest a new physiopatholoic mechanism involving abnormally accelerated centripetal migration of peripheral ECs that accumulate in the centre of the cornea, resulting in the slow formation of the plaque-like endothelial structure, typical of FCED.

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