blindness caused by deficiency in ae3 chloridebicarbonate exchanger不足造成的失明ae3 chloridebicarbonate换热器.pdfVIP

Blindness Caused by Deficiency in AE3 Chloride/ Bicarbonate Exchanger 1,2 3 3 2 4 1,2 ´2,3 Bernardo V. Alvarez , Gregory S. Gilmour , Silvina C. Mema , Brent T. Martin , Gary E. Shull , Joseph R. Casey , Yves Sauve * 1 Membrane Protein Research Group, Department of Biochemistry, University of Alberta, Edmonton, Canada, 2 Department of Physiology, University of Alberta, Edmonton, Canada, 3 Department of Ophthalmology, University of Alberta, Edmonton, Canada, 4 Departments of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America Background. Vision is initiated by phototransduction in the outer retina by photoreceptors, whose high metabolic rate generates large CO loads. Inner retina cells then process the visual signal and CO . The anion exchanger 3 gene (AE3/ 2 2 Slc4a3) encodes full-length AE3 (AE3fl) and cardiac AE3 (AE3c) isoforms, catalyzing plasma membrane Cl2/HCO32 exchange ¨ in Muller (AE3fl) and horizontal (AE3c) cells. AE3 thus maintains acid-balance by removing photoreceptor-generated CO2 waste. Methodology/Principal Findings. We report that Slc4a32/ 2 null mice have inner retina defects (electroretinogram b-wave reduction, optic nerve and retinal vessel anomalies). These pathologic features are common to most human vitreoretinal degenerations. Immunobloting analysis revealed that Na+/HCO32 co-transporter (NBC1), and carbonic anhydrase II and CAXIV, protein expression were elevated in Slc4a32/ 2