The Molecular Basis of Fuchs' Endothelial Corneal Dystrophy

Fuchs' endothelial corneal dystrophy (FECD) is a common disease resulting from corneal endothelial cell dysfunction. It is inherited in an autosomal dominant fashion with incomplete penetrance, and with a female bias. Approximately half of cases occur sporadically, and the remainder are familial. Early and late-onset forms of the disease exist. A review of the literature has revealed more than 15 genes harbouring mutations and/or single nucleotide polymorphisms associated with FECD. The proteins encoded by these genes cover a wide range of endothelial function, including transcription regulation, DNA repair, mitochondrial DNA mutations, targeting of proteins to the cell membrane, deglutamylation of proteins, extracellular matrix secretion, formation of cell-cell and cell-extracellular matrix junctions, water pump, and apoptosis. These genetic variations will form the platform for the further understanding of the pathological basis of the disease, and the development of targeted treatments. This review aims to summarise known genetic variations associated with FECD, discuss any known molecular effects of the variations, how these provide opportunities for targeted therapies, and what therapies are currently in development.