Inner retinal photoreception independent of the visual retinoid cycle.
Mice lacking the visual cycle enzymes RPE65 or lecithin-retinol acyl transferase (Lrat) have pupillary light responses (PLR) that are less sensitive than those of mice with outer retinal degeneration (rd/rd or rdta). Inner retinal photoresponses are mediated by melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs), suggesting that the melanopsin-dependent photocycle utilizes RPE65 and Lrat. To test this hypothesis, we generated rpe65(-/-); rdta and lrat(-/-); rd/rd mutant mice. Unexpectedly, both rpe65(-/-); rdta and lrat(-/-); rd/rd mice demonstrate paradoxically increased PLR photosensitivity compared with mice mutant in visual cycle enzymes alone. Acute pharmacologic inhibition of the visual cycle of melanopsin-deficient mice with all-trans-retinylamine results in a near-total loss of PLR sensitivity, whereas treatment of rd/rd mice has no effect, demonstrating that the inner retina does not require the visual cycle. Treatment of rpe65(-/-); rdta with 9-cis-retinal partially restores PLR sensitivity. Photic sensitivity in P8 rpe65(-/-) and lrat(-/-) ipRGCs is intact as measured by ex vivo multielectrode array recording. These results demonstrate that the melanopsin-dependent ipRGC photocycle is independent of the visual retinoid cycle.
Tu
Daniel C
DC
Departments of *Ophthalmology and Visual Sciences and.
Owens
Leah A
LA
Departments of *Ophthalmology and Visual Sciences and.
Anderson
Lauren
L
Departments of *Ophthalmology and Visual Sciences and.
Golczak
Marcin
M
Department of Pharmacology, Case Western Reserve School of Medicine, Cleveland, OH 44106-4965.
Doyle
Susan E
SE
Department of Biology, University of Virginia, Charlottesville, VA 22904.
McCall
Maureen
M
and Departments of Ophthalmology and Visual Sciences and Psychological and Brain Sciences, University of Louisville, Louisville, KY 40292.
Menaker
Michael
M
Department of Biology, University of Virginia, Charlottesville, VA 22904.
Palczewski
Krzysztof
K
Department of Pharmacology, Case Western Reserve School of Medicine, Cleveland, OH 44106-4965.
Van Gelder
Russell N
RN
Departments of *Ophthalmology and Visual Sciences and vangelder@vision.wustl.edu.|Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, MO 63110.
D000818:Animals; D002352:Carrier Proteins; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011680:Pupil; D012160:Retina / Q000473:pathology / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D012176:Retinoids / Q000378:metabolism*; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; D000099210:Melanopsin
D002352:Carrier Proteins; D005136:Eye Proteins; D012176:Retinoids; D017299:Rod Opsins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; D000099210:Melanopsin