TY - JOUR
T1 - Inner retinal photoreception independent of the visual retinoid cycle
AU - Tu, Daniel C.
AU - Owens, Leah A.
AU - Anderson, Lauren
AU - Golczak, Marcin
AU - Doyle, Susan E.
AU - McCall, Maureen
AU - Menaker, Michael
AU - Palczewski, Krzysztof
AU - Van Gelder, Russell N.
PY - 2006/7/4
Y1 - 2006/7/4
N2 - 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 Irat-/-; rd/rd mutant mice. Unexpectedly, both rpe65-/-; rdta and Irat -/-; 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 Irat-/- 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.
AB - 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 Irat-/-; rd/rd mutant mice. Unexpectedly, both rpe65-/-; rdta and Irat -/-; 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 Irat-/- 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.
KW - Melanopsin
KW - Pupillary light response
KW - Retinal degeneration
KW - Retinal ganglion cell
KW - Visual photocycle
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U2 - 10.1073/pnas.0600917103
DO - 10.1073/pnas.0600917103
M3 - Article
C2 - 16788071
AN - SCOPUS:33745914966
SN - 0027-8424
VL - 103
SP - 10426
EP - 10431
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 27
ER -