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Russell N. Van Gelder, Tamara Lamprecht, Kareem Mawad, Timothy Sexton, Xudong Qiu; Mechanisms of murine melanopsin-mediated photoreception. Journal of Vision 2009;9(14):25. doi: https://doi.org/10.1167/9.14.25.
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The mammalian inner retina harbors a small number of intrinsically photosensitive ganglion cells (ipRGCs). These cells utilize melanopsin as their photopigment. Initial studies of melanopsin knockout mice demonstrated that these animals retained the ability to entrain their circadian rhythms and constrict their pupils to light. Subsequent analysis has demonstrated that ipRGCs can both transduce outer retinal signaling to hypothalamic and pretectal brain areas, as well as signal by intrinsic photosensitivity.
We have been interested in the physiologic properties that melanopsin adds to outer retinal signaling, which presumably have been the basis of evolutionary selection maintaining inner retinal photosensivity. With respect to the pupillary light response, we have found that melanopsin is necessary for maintenance of constriction under constant bright field conditions. With respect to circadian entrainment, we find that while under ‘equatorial’ LD 12:12 conditions, melanopsin-deficient mice resemble wild-type animals, when placed under simulated photoperiodic lighting cycles, these animals display a variety of abnormal entrainment phenotypes not seen in wild-type or outer retinal blind (rd/rd) animals. Melanopsin-deficient mice also show marked behavioral abnormalities following severe phase shifting stimuli.
We have also investigated the nature of melanopsin photocycle. Earlier work from our laboratory indicated that melanopsin functions independent of the outer retinal photocycle. Recent work from other laboratories has suggested that melanopsin is a bistable photopigment. However, our attempts to demonstrate bistability in mouse ipRGC in vitro recordings have been unsuccessful. Using ultraviolet depletion of retinoids in vitro we find evidence for autonomous regeneration of photopigment in dark.
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