In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa.
Genetic and environmental factors modify the severity of human neurodegenerations. Retinal degenerations caused by rhodopsin gene mutations show severity differences within and between families and even within regions of the same eye. Environmental light is thought to contribute to this variation. In the naturally occurring dog model of the human disorder, we found that modest light levels, as used in routine clinical practice, dramatically accelerated the neurodegeneration. Dynamics of acute retinal injury (consisting of abnormal intraretinal light scattering) were visualized in vivo in real time with high-resolution optical imaging. Long term consequences included fast or slow retinal degeneration or repair of injury depending on the dose of light exposure. These experiments provide a platform to study mechanisms of neuronal injury, repair, compensation, and degeneration. The data also argue for a gene-specific clinical trial of light reduction in human rhodopsin disease.
Cideciyan
Artur V
AV
Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA. cideciya@mail.med.upenn.edu
Jacobson
Samuel G
SG
Aleman
Tomas S
TS
Gu
Danian
D
Pearce-Kelling
Susan E
SE
Sumaroka
Alexander
A
Acland
Gregory M
GM
Aguirre
Gustavo D
GD
D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D008027:Light; D009154:Mutation; D009416:Nerve Regeneration; D012160:Retina / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D012243:Rhodopsin / Q000235:genetics* / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism
D018808:Transcription Factor AP-1; D004247:DNA; D012243:Rhodopsin