Journal
HUMAN MOLECULAR GENETICS
Volume 14, Issue 2, Pages 255-265Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddi023
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Funding
- NCRR NIH HHS [M01-RR00064] Funding Source: Medline
- NEI NIH HHS [R01EY14428, EY08123, R01EY14448] Funding Source: Medline
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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.
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