Journal article
Human cone photoreceptor dependence on RPE65 isomerase
Proceedings of the National Academy of Sciences - PNAS, Vol.104(38), pp.15123-15128
09/18/2007
DOI: 10.1073/pnas.0706367104
PMCID: PMC1986623
PMID: 17848510
Abstract
The visual (retinoid) cycle, the enzymatic pathway that regenerates chromophore after light absorption, is located primarily in the retinal pigment epithelium (RPE) and is essential for rod photoreceptor survival. Whether this pathway also is essential for cone photoreceptor survival is unknown, and there are no data from man or monkey to address this question. The visual cycle is naturally disrupted in humans with Leber congenital amaurosis (LCA), which is caused by mutations in RPE65, the gene that encodes the retinoid isomerase. We investigated such patients over a wide age range (3-52 years) for effects on the cone-rich human fovea. In vivo microscopy of the fovea showed that, even at the youngest ages, patients with RPE65-LCA exhibited cone photoreceptor loss. This loss was incomplete, however, and residual cone photoreceptor structure and function persisted for decades. Basic questions about localization of RPE65 and isomerase activity in the primate eye were addressed by examining normal macaque. RPE65 was definitively localized by immunocytochemistry to the central RPE and, by immunoblotting, appeared to concentrate in the central retina. The central retinal RPE layer also showed a 4-fold higher retinoid isomerase activity than more peripheral RPE. Early cone photoreceptor losses in RPE65-LCA suggest that robust RPE65-based visual chromophore production is important for cones; the residual retained cone structure and function support the speculation that alternative pathways are critical for cone photoreceptor survival.
Details
- Title: Subtitle
- Human cone photoreceptor dependence on RPE65 isomerase
- Creators
- Samuel G Jacobson - Scheie Eye Institute, Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. jacobsos@mail.med.upenn.eduTomas S AlemanArtur V CideciyanElise HeonMarcin GolczakWilliam A BeltranAlexander SumarokaSharon B SchwartzAlejandro J RomanElizabeth A M WindsorJames M WilsonGustavo D AguirreEdwin M StoneKrzysztof Palczewski
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.104(38), pp.15123-15128
- DOI
- 10.1073/pnas.0706367104
- PMID
- 17848510
- PMCID
- PMC1986623
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- United States
- Grant note
- P30 EY011373 / NEI NIH HHS U10 EY017280 / NEI NIH HHS EY017280 / NEI NIH HHS P30 EY011373-119005 / NEI NIH HHS R01 EY009339 / NEI NIH HHS R01 EY009339-18 / NEI NIH HHS P30 EY11373 / NEI NIH HHS EY09339 / NEI NIH HHS
- Language
- English
- Date published
- 09/18/2007
- Academic Unit
- Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980288002771
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