Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration
Open Access
- 24 November 2004
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 14 (2), 255-265
- https://doi.org/10.1093/hmg/ddi023
Abstract
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.Keywords
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