Journal Article

Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration

Zhenglin Yang, Bernardo V. Alvarez, Christina Chakarova, Li Jiang, Goutam Karan, Jeanne M. Frederick, Yu Zhao, Yves Sauvé, Xi Li, Eberhart Zrenner, Bernd Wissinger, Anneke I. Den Hollander, Bradley Katz, Wolfgang Baehr, Frans P. Cremers, Joseph R. Casey, Shomi S. Bhattacharya and Kang Zhang

in Human Molecular Genetics

Volume 14, issue 2, pages 255-265
Published in print January 2005 | ISSN: 0964-6906
Published online November 2004 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddi023
Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration

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Retina and retinal pigment epithelium (RPE) belong to the metabolically most active tissues in the human body. Efficient removal of acid load from retina and RPE is a critical function mediated by the choriocapillaris. However, the mechanism by which pH homeostasis is maintained is largely unknown. Here, we show that a functional complex of carbonic anhydrase 4 (CA4) and Na+/bicarbonate co-transporter 1 (NBC1) is specifically expressed in the choriocapillaris and that missense mutations in CA4 linked to autosomal dominant rod–cone dystrophy disrupt NBC1-mediated HCO3 transport. Our results identify a novel pathogenic pathway in which a defect in a functional complex involved in maintaining pH balances, but not expressed in retina or RPE, leads to photoreceptor degeneration. The importance of a functional CA4 for survival of photoreceptors implies that CA inhibitors, which are widely used as medications, particularly in the treatment of glaucoma, may have long-term adverse effects on vision.

Journal Article.  7826 words.  Illustrated.

Subjects: Genetics and Genomics

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