Inner retinal photoreception independent of the visual retinoid cycle

Daniel C. Tu, Leah A. Owens, Lauren Anderson, Marcin Golczak, Susan E. Doyle, Maureen McCall, Michael Menaker, Krzysztof Palczewski, Russell N. Van Gelder

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)10426-10431
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number27
StatePublished - Jul 4 2006
Externally publishedYes


  • Melanopsin
  • Pupillary light response
  • Retinal degeneration
  • Retinal ganglion cell
  • Visual photocycle

ASJC Scopus subject areas

  • General


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