title: SLC4A11 and the Pathophysiology of Congenital Hereditary Endothelial Dystrophy.
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.
authors.affiliation: Department of Ophthalmology, Ross Eye Institute, School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, 1176 Main Street, Buffalo, NY 14209, USA ; SUNY Eye Institute, Buffalo, NY 14214, USA ; Research Service, Veterans Administration Western New York Healthcare System (VAWNYHS), Building 20, 3495 Bailey Avenue, Buffalo, NY 14215, USA.
authors.forename: Sangita P
authors.initials: SP
authors.lastname: Patel
authors.affiliation: Department of Ophthalmology, Ross Eye Institute, School of Medicine and Biomedical Sciences, The State University of New York at Buffalo, 1176 Main Street, Buffalo, NY 14209, USA ; SUNY Eye Institute, Buffalo, NY 14214, USA ; Department of Physiology and Biophysics, The State University of New York at Buffalo, 124 Sherman Hall, Buffalo, NY 14214, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Parker
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D017920:Antiporters / Q000235:genetics* / Q000378:metabolism*; D003317:Corneal Dystrophies, Hereditary / Q000503:physiopathology*; D019573:Epithelium, Corneal / Q000378:metabolism*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D015994:Incidence; D015640:Ion Channel Gating; D051379:Mice; D008954:Models, Biological; D012307:Risk Factors
chemical_list: D027321:Anion Transport Proteins; D017920:Antiporters; D005819:Genetic Markers; C425809:SLC4A11 protein, human