Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration.
The death of photoreceptor cells caused by retinal degenerative diseases often results in a complete loss of retinal responses to light. We explore the feasibility of converting inner retinal neurons to photosensitive cells as a possible strategy for imparting light sensitivity to retinas lacking rods and cones. Using delivery by an adeno-associated viral vector, here, we show that long-term expression of a microbial-type rhodopsin, channelrhodopsin-2 (ChR2), can be achieved in rodent inner retinal neurons in vivo. Furthermore, we demonstrate that expression of ChR2 in surviving inner retinal neurons of a mouse with photoreceptor degeneration can restore the ability of the retina to encode light signals and transmit the light signals to the visual cortex. Thus, expression of microbial-type channelrhodopsins, such as ChR2, in surviving inner retinal neurons is a potential strategy for the restoration of vision after rod and cone degeneration.
Bi
Anding
A
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Cui
Jinjuan
J
Ma
Yu-Ping
YP
Olshevskaya
Elena
E
Pu
Mingliang
M
Dizhoor
Alexander M
AM
Pan
Zhuo-Hua
ZH
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005074:Evoked Potentials, Visual / Q000235:genetics / Q000528:radiation effects; D015870:Gene Expression / Q000502:physiology*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D010775:Photic Stimulation / Q000379:methods; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000235:genetics; D012160:Retina / Q000166:cytology; D012162:Retinal Degeneration / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D012243:Rhodopsin / Q000502:physiology*; D014795:Visual Pathways / Q000502:physiology
D049452:Green Fluorescent Proteins; D012243:Rhodopsin