Dysmorphic photoreceptors in a P23H mutant rhodopsin model of retinitis pigmentosa are metabolically active and capable of regenerating to reverse retinal degeneration.
This study evaluated the capacity of Xenopus laevis retina to regenerate photoreceptor cells after cyclic light-mediated acute rod photoreceptor degeneration in a transgenic P23H mutant rhodopsin model of retinits pigmentosa. After discontinuation of cyclic light exposure, we monitored histologic progression of retinal regeneration over a 3 week recovery period. To assess their metabolomic states, contralateral eyes were processed for computational molecular phenotyping. We found that retinal degeneration in the P23H rhodopsin mutation could be partially reversed, with regeneration of rod photoreceptors recovering normal morphology (including full-length rod outer segments) by the end of the 3 week recovery period. In contrast, retinal degeneration mediated by directly induced apoptosis did not recover in the 3 week recovery period. Dystrophic rod photoreceptors with truncated rod outer segments were identified as the likely source of rod photoreceptor regeneration in the P23H retinas. These dystrophic photoreceptors remain metabolically active despite having lost most of their outer segments.
Department of Ophthalmology and Visual Sciences and Centre for Macular Research, University of British Columbia, Vancouver, British Columbia, Canada, V5Z 3N9.
Damian C
DC
Lee
Felix R
FR
Vazquez-Chona
W Drew
WD
Ferrell
Beatrice M
BM
Tam
Bryan W
BW
Jones
Robert E
RE
Marc
Orson L
OL
Moritz
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D006639:Histidine / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009416:Nerve Regeneration / Q000235:genetics; D011392:Proline / Q000235:genetics; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism* / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000378:metabolism; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014982:Xenopus laevis
D006639:Histidine; D012243:Rhodopsin; D011392:Proline