Skip Navigation


Human Molecular Genetics Advance Access originally published online on November 24, 2004
Human Molecular Genetics 2005 14(2):255-265; doi:10.1093/hmg/ddi023
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Material
Right arrow All Versions of this Article:
14/2/255    most recent
ddi023v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (9)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Yang, Z.
Right arrow Articles by Zhang, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, Z.
Right arrow Articles by Zhang, K.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, Vol. 14, No. 2 © Oxford University Press 2005; all rights reserved

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

Zhenglin Yang1,2,{dagger}, Bernardo V. Alvarez5,{dagger}, Christina Chakarova6,{dagger}, Li Jiang1,2, Goutam Karan1,2, Jeanne M. Frederick1, Yu Zhao1,2, Yves Sauvé1, Xi Li1,2, Eberhart Zrenner7, Bernd Wissinger7, Anneke I. Den Hollander8, Bradley Katz1, Wolfgang Baehr1,3,4, Frans P. Cremers8, Joseph R. Casey5, Shomi S. Bhattacharya6 and Kang Zhang1,2,4,*

1Department of Ophthalmology and Visual Science, University of Utah Health Science Center, Salt Lake City, UT 84112, USA, 2Program in Human Molecular Biology and Genetics, Eccles Institute of Human Genetics and 3Department of Biology and 4Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT 84112, USA, 5CIHR Group in Molecular Biology of Membrane Proteins, Department of Physiology, University of Alberta, Edmonton, Canada T6G 2H7 and 6Department of Molecular Genetics, Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EV, UK, 7Universitätsaugenklinik Tübingen, Abt. Pathophysiologie des Sehens und Neuroophthalmologie, Tübingen, Germany and 8Department of Human Genetics, University Medical Centre Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands

* To whom correspondence should be addressed. Tel: +1 8015856797; Fax: +1 8015853501; Email: kzhang{at}hmbg.utah.edu

Received September 16, 2004; Revised October 19, 2004; Accepted November 10, 2004

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.

{dagger} The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 IOVSHome page
T. Baba, R. Grebe, T. Hasegawa, I. Bhutto, C. Merges, D. S. McLeod, and G. A. Lutty
Maturation of the Fetal Human Choriocapillaris
Invest. Ophthalmol. Vis. Sci., July 1, 2009; 50(7): 3503 - 3511.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
N. Svichar, A. Waheed, W. S. Sly, J. C. Hennings, C. A. Hubner, and M. Chesler
Carbonic Anhydrases CA4 and CA14 Both Enhance AE3-Mediated Cl--HCOFormula Exchange in Hippocampal Neurons
J. Neurosci., March 11, 2009; 29(10): 3252 - 3258.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Datta, A. Waheed, G. Bonapace, G. N. Shah, and W. S. Sly
Pathogenesis of retinitis pigmentosa associated with apoptosis-inducing mutations in carbonic anhydrase IV
PNAS, March 3, 2009; 106(9): 3437 - 3442.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
L. Kohn, M. S. I. Burstedt, F. Jonsson, K. Kadzhaev, E. Haamer, O. Sandgren, and I. Golovleva
Carrier of R14W in Carbonic Anhydrase IV Presents Bothnia Dystrophy Phenotype Caused by Two Allelic Mutations in RLBP1
Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 3172 - 3177.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
D. Trifunovic, M. Karali, D. Camposampiero, D. Ponzin, S. Banfi, and V. Marigo
A High-Resolution RNA Expression Atlas of Retinitis Pigmentosa Genes in Human and Mouse Retinas
Invest. Ophthalmol. Vis. Sci., June 1, 2008; 49(6): 2330 - 2336.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
Z. Qu and H. C. Hartzell
Bestrophin Cl- channels are highly permeable to HCO3-
Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1371 - C1377.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
B. V. Alvarez, E. N. Vithana, Z. Yang, A. H. Koh, K. Yeung, V. Yong, H. J. Shandro, Y. Chen, P. Kolatkar, P. Palasingam, et al.
Identification and Characterization of a Novel Mutation in the Carbonic Anhydrase IV Gene that Causes Retinitis Pigmentosa
Invest. Ophthalmol. Vis. Sci., August 1, 2007; 48(8): 3459 - 3468.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. M. Ogilvie, K. K. Ohlemiller, G. N. Shah, B. Ulmasov, T. A. Becker, A. Waheed, A. K. Hennig, P. D. Lukasiewicz, and W. S. Sly
Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response
PNAS, May 15, 2007; 104(20): 8514 - 8519.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
A. Pushkin and I. Kurtz
SLC4 base (HCO3-, CO32-) transporters: classification, function, structure, genetic diseases, and knockout models
Am J Physiol Renal Physiol, March 1, 2006; 290(3): F580 - F599.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.