PURPOSE: To characterize the influence of light and vitamin A on retinal degeneration in an animal model of retinitis pigmentosa caused by the rhodopsin P23H mutation. METHODS: Retinal degeneration was examined in transgenic Xenopus laevis expressing P23H rhodopsin, in which retinal degeneration is completely rescued by preventing light exposure. The sensitivity of this retinal degeneration to varying intensities, wavelengths, and durations of light exposure, and to vitamin A deprivation was characterized. RESULTS: Green light was the most effective inducer of retinal degeneration in this model. Retinal degeneration was induced by prolonged exposure to green light and was prevented by filters that block short wavelengths. Reducing the duration of light exposure prevented retinal degeneration, even when the light intensity was proportionally increased. Vitamin A deprivation also induced retinal degeneration associated with defects in P23H rhodopsin biosynthesis. Vitamin A deprivation did not cause retinal degeneration in nontransgenic animals. CONCLUSIONS: The mechanism of retinal degeneration in this animal model of RP involves the interaction of light with rhodopsin rather than with free chromophore or bleached rhodopsin. These results may explain the clinical benefits of vitamin A for patients with retinitis pigmentosa and may indicate that pharmacological chaperones are a viable approach to RP therapy. Results also suggest strategies for minimizing RD in patients through controlling light exposure duration or wavelengths.
PURPOSE: To characterize the influence of light and vitamin A on retinal degeneration in an animal model of retinitis pigmentosa caused by the rhodopsinP23H mutation. METHODS:Retinal degeneration was examined in transgenic Xenopus laevis expressing P23Hrhodopsin, in which retinal degeneration is completely rescued by preventing light exposure. The sensitivity of this retinal degeneration to varying intensities, wavelengths, and durations of light exposure, and to vitamin A deprivation was characterized. RESULTS: Green light was the most effective inducer of retinal degeneration in this model. Retinal degeneration was induced by prolonged exposure to green light and was prevented by filters that block short wavelengths. Reducing the duration of light exposure prevented retinal degeneration, even when the light intensity was proportionally increased. Vitamin A deprivation also induced retinal degeneration associated with defects in P23Hrhodopsin biosynthesis. Vitamin A deprivation did not cause retinal degeneration in nontransgenic animals. CONCLUSIONS: The mechanism of retinal degeneration in this animal model of RP involves the interaction of light with rhodopsin rather than with free chromophore or bleached rhodopsin. These results may explain the clinical benefits of vitamin A for patients with retinitis pigmentosa and may indicate that pharmacological chaperones are a viable approach to RP therapy. Results also suggest strategies for minimizing RD in patients through controlling light exposure duration or wavelengths.
Authors: Wei Wang; Sang Joon Lee; Patrick A Scott; Xiaoqin Lu; Douglas Emery; Yongqin Liu; Toshihiko Ezashi; Michael R Roberts; Jason W Ross; Henry J Kaplan; Douglas C Dean Journal: Cell Rep Date: 2016-03-31 Impact factor: 9.423
Authors: Ruanne Y J Vent-Schmidt; Runxia H Wen; Zusheng Zong; Colette N Chiu; Beatrice M Tam; Christopher G May; Orson L Moritz Journal: J Neurosci Date: 2017-01-25 Impact factor: 6.167
Authors: Sanae Sakami; Tadao Maeda; Grzegorz Bereta; Kiichiro Okano; Marcin Golczak; Alexander Sumaroka; Alejandro J Roman; Artur V Cideciyan; Samuel G Jacobson; Krzysztof Palczewski Journal: J Biol Chem Date: 2011-01-11 Impact factor: 5.157