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. |