Journal article
Increased Light Exposure Alleviates One Form of Photoreceptor Degeneration Marked by Elevated Calcium in the Dark
PloS one, v 4(12), 8438
24 Dec 2009
PMID: 20041177
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: In one group of gene mutations that cause photoreceptor degeneration in human patients, guanylyl cyclase is overactive in the dark. The ensuing excess opening of cGMP-gated cation channels causes intracellular calcium to rise to toxic levels. The Y99C mutation in guanylate cyclase-activating protein 1 (GCAP1) has been shown to act this way. We determined whether prolonged light exposure, which lowers cGMP levels through activation of phototransduction, might protect photoreceptors in a line of transgenic mice carrying the GCAP1-Y99C.
Methodology/Principal Findings: We reared cohorts of GCAP1-Y99C transgenic mice under standard cyclic, constant dark and constant light conditions. Mouse eyes were analyzed by histology and by immunofluorescence for GFAP upregulation, a non-specific marker for photoreceptor degeneration. Full-field electroretinograms (ERGs) were recorded to assess retinal function. Consistent with our hypothesis, constant darkness accelerated disease, while continuous lighting arrested photoreceptor degeneration.
Conclusions/Significance: In contrast to most forms of retinal degeneration, which are exacerbated by increased exposure to ambient light, a subset with mutations that cause overly active guanylyl cyclase and high intracellular calcium benefitted from prolonged light exposure. These findings may have therapeutic implications for patients with these types of genetic defects.
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Details
- Title
- Increased Light Exposure Alleviates One Form of Photoreceptor Degeneration Marked by Elevated Calcium in the Dark
- Creators
- Xiaoqing Liu - Massachusetts Eye and Ear InfirmaryBasil S. Pawlyk - Massachusetts Eye and Ear InfirmaryMichael Adamian - Massachusetts Eye and Ear InfirmaryElena V. Olshevskaya - Salus UniversityAlexander M. Dizhoor - Salus UniversityClint L. Makino - Massachusetts Eye and Ear InfirmaryTiansen Li - National Eye Institute
- Publication Details
- PloS one, v 4(12), 8438
- Publisher
- Public Library of Science
- Number of pages
- 6
- Grant note
- Foundation Fighting Blindness Macular Vision Research Foundation EY10309; EY10581; EY11522; EY12944; EY14104 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pennsylvania College of Optometry (PCO)
- Web of Science ID
- WOS:000273104000007
- Scopus ID
- 2-s2.0-77949505966
- Other Identifier
- 991022035116004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Ophthalmology