Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin.
The rod and cone cells of the mammalian retina are the principal photoreceptors for image-forming vision. They transmit information by means of a chain of intermediate cells to the retinal ganglion cells, which in turn send signals from the retina to the brain. Loss of photoreceptor cells, as happens in a number of human diseases, leads to irreversible blindness. In a mouse model (rd/rd) of photoreceptor degeneration, we used a viral vector to express in a large number of retinal ganglion cells the light sensitive protein melanopsin, normally present in only a specialized subset of the cells. Whole-cell patch-clamp recording showed photoresponses in these cells even after degeneration of the photoreceptors and additional pharmacological or Cd(2+) block of synaptic function. Interestingly, similar responses were observed across a wide variety of diverse types of ganglion cell of the retina. The newly melanopsin-expressing ganglion cells provided an enhancement of visual function in rd/rd mice: the pupillary light reflex (PLR) returned almost to normal; the mice showed behavioral avoidance of light in an open-field test, and they could discriminate a light stimulus from a dark one in a two-choice visual discrimination alley. Recovery of the PLR was stable for at least 11 months. It has recently been shown that ectopic retinal expression of a light sensitive bacterial protein, channelrhodopsin-2, can restore neuronal responsiveness and simple visual abilities in rd/rd mice. For therapy in human photodegenerations, channelrhodopsin-2 and melanopsin have different advantages and disadvantages; both proteins (or modifications of them) should be candidates.
Lin
Bin
B
Massachusetts General Hospital, Harvard Medical School, Thier 429, 50 Blossom Street, Boston, MA 02114, USA.
Koizumi
Amane
A
Tanaka
Nobushige
N
Panda
Satchidananda
S
Masland
Richard H
RH
D000818:Animals; D008027:Light; D051379:Mice; D010775:Photic Stimulation; D020419:Photoreceptor Cells, Vertebrate; D012162:Retinal Degeneration / Q000628:therapy*; D012165:Retinal Ganglion Cells / Q000378:metabolism; D017299:Rod Opsins / Q000008:administration & dosage / Q000235:genetics* / Q000627:therapeutic use; D014161:Transduction, Genetic; D014785:Vision, Ocular / Q000235:genetics*; D000099210:Melanopsin
D017299:Rod Opsins; D000099210:Melanopsin