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Publication : Inner retinal photoreception independent of the visual retinoid cycle.

First Author  Tu DC Year  2006
Journal  Proc Natl Acad Sci U S A Volume  103
Issue  27 Pages  10426-31
PubMed ID  16788071 Mgi Jnum  J:111700
Mgi Id  MGI:3654741 Doi  10.1073/pnas.0600917103
Citation  Tu DC, et al. (2006) Inner retinal photoreception independent of the visual retinoid cycle. Proc Natl Acad Sci U S A 103(27):10426-31
abstractText  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.
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