Inner retinal photoreception independent of the visual retinoid cycle

Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10426-10431. doi: 10.1073/pnas.0600917103. Epub 2006 Jun 20.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins
  • Eye Proteins / genetics
  • Eye Proteins / metabolism
  • Light
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutation / genetics
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology
  • Pupil
  • Retina / pathology
  • Retina / physiology*
  • Retinal Ganglion Cells / metabolism*
  • Retinoids / metabolism*
  • Rod Opsins / genetics
  • Rod Opsins / metabolism
  • Vision, Ocular / physiology*
  • cis-trans-Isomerases


  • Carrier Proteins
  • Eye Proteins
  • Retinoids
  • Rod Opsins
  • melanopsin
  • retinoid isomerohydrolase
  • cis-trans-Isomerases