Increased light exposure alleviates one form of photoreceptor degeneration marked by elevated calcium in the dark.
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-activat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-12-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2793020?pdf=render |
| _version_ | 1828530045974478848 |
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| author | Xiaoqing Liu Basil S Pawlyk Michael Adamian Elena V Olshevskaya Alexander M Dizhoor Clint L Makino Tiansen Li |
| author_facet | Xiaoqing Liu Basil S Pawlyk Michael Adamian Elena V Olshevskaya Alexander M Dizhoor Clint L Makino Tiansen Li |
| author_sort | Xiaoqing Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T22:17:32Z |
| format | Article |
| id | doaj.art-dce95639d6754e07b1a9474ab42aba13 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T22:17:32Z |
| publishDate | 2009-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-dce95639d6754e07b1a9474ab42aba132022-12-22T00:48:34ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-12-01412e843810.1371/journal.pone.0008438Increased light exposure alleviates one form of photoreceptor degeneration marked by elevated calcium in the dark.Xiaoqing LiuBasil S PawlykMichael AdamianElena V OlshevskayaAlexander M DizhoorClint L MakinoTiansen LiBACKGROUND: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.http://europepmc.org/articles/PMC2793020?pdf=render |
| spellingShingle | Xiaoqing Liu Basil S Pawlyk Michael Adamian Elena V Olshevskaya Alexander M Dizhoor Clint L Makino Tiansen Li Increased light exposure alleviates one form of photoreceptor degeneration marked by elevated calcium in the dark. PLoS ONE |
| title | Increased light exposure alleviates one form of photoreceptor degeneration marked by elevated calcium in the dark. |
| title_full | Increased light exposure alleviates one form of photoreceptor degeneration marked by elevated calcium in the dark. |
| title_fullStr | Increased light exposure alleviates one form of photoreceptor degeneration marked by elevated calcium in the dark. |
| title_full_unstemmed | Increased light exposure alleviates one form of photoreceptor degeneration marked by elevated calcium in the dark. |
| title_short | Increased light exposure alleviates one form of photoreceptor degeneration marked by elevated calcium in the dark. |
| title_sort | increased light exposure alleviates one form of photoreceptor degeneration marked by elevated calcium in the dark |
| url | http://europepmc.org/articles/PMC2793020?pdf=render |
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