SLC4A11 and the Pathophysiology of Congenital Hereditary Endothelial Dystrophy.

Sangita P Patel,Mark D Parker

doi:10.1155/2015/475392

Abstract

Congenital hereditary endothelial dystrophy (CHED) is a rare autosomal recessive disorder of the corneal endothelium characterized by nonprogressive bilateral corneal edema and opacification present at birth. Here we review the current knowledge on the role of the SLC4A11 gene, protein, and its mutations in the pathophysiology and clinical presentation of CHED. Individuals with CHED have mutations in SLC4A11 which encodes a transmembrane protein in the SLC4 family of bicarbonate transporters. The expression of SLC4A11 in the corneal endothelium and inner ear patterns the deficits seen in CHED with corneal edema and hearing loss (Harboyan syndrome). slc4a11-null-mouse models recapitulate the CHED disease phenotype, thus establishing a functional role for SLC4A11 in CHED. However, the transport function of SLC4A11 remains unsettled. Some of the roles that have been attributed to SLC4A11 include H+ and NH4 + permeation, electrogenic Na+-H+ exchange, and water transport. Future studies of the consequences of SLC4A11 dysfunction as well as further understanding of corneal endothelial ion transport will help clarify the involvement of SLC4A11 in the pathophysiology of CHED.

Highlights

Congenital hereditary endothelial dystrophy (CHED) is a rare disorder of the corneal endothelium with an early onset of corneal edema
Recent genetic analyses and review of clinical findings confirm that the previously termed autosomal dominant CHED is a form of posterior polymorphous corneal dystrophy with early and severe corneal edema [2]. It is no longer considered in the category of CHED
This review focuses on the role of SLC4A11 in the pathophysiologic mechanisms and clinical presentation of CHED

Summary

Introduction

Congenital hereditary endothelial dystrophy (CHED) is a rare disorder of the corneal endothelium with an early onset of corneal edema. Recent genetic analyses and review of clinical findings confirm that the previously termed autosomal dominant CHED (originally CHED1) is a form of posterior polymorphous corneal dystrophy with early and severe corneal edema [2]. It is no longer considered in the category of CHED (i.e., the entity CHED1 is classified with posterior polymorphous corneal dystrophy). Based on the 2015 update to the International Classification of Corneal Dystrophies, the term “CHED” exclusively refers to autosomal recessive CHED (originally CHED2) [3]. This review focuses on the role of SLC4A11 in the pathophysiologic mechanisms and clinical presentation of CHED

Mutations in SLC4A11

Clinical Phenotype and Molecular Expression

The Molecular Actions of SLC4A11

The Role of SLC4A11 in the Cornea

The Contribution of SLC4A11 Dysfunction to CHED

Conclusion