The dependence of retinal degeneration caused by the rhodopsin P23H mutation on light exposure and vitamin a deprivation.
OBJECTIVE
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.
Tam
Beatrice M
BM
Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Qazalbash
Ali
A
Lee
Hak-Choel
HC
Moritz
Orson L
OL
D000818:Animals; D030801:Animals, Genetically Modified; D008027:Light; D008297:Male; D018613:Microscopy, Confocal; D020125:Mutation, Missense; D010783:Photometry; D011833:Radiation Injuries, Experimental / Q000209:etiology* / Q000235:genetics; D012160:Retina / Q000528:radiation effects; D012162:Retinal Degeneration / Q000209:etiology* / Q000235:genetics; D012243:Rhodopsin / Q000235:genetics* / Q000528:radiation effects*; D019076:Transgenes; D014801:Vitamin A / Q000502:physiology; D014802:Vitamin A Deficiency / Q000150:complications*; D014982:Xenopus laevis
D014801:Vitamin A; D012243:Rhodopsin