Rodents blind from outer retinal (rod and cone) degeneration still retain several light-dependent phenomena, including entrainment of the circadian clock and pupillary light responsiveness. This paradox is explained by the presence of intrinsically photosensitive retinal ganglion cells in the inner retina. These cells have unique properties, including a novel action spectrum, resistance to bleaching and adaptation under continuous light, and resistance to vitamin A depletion. Two candidate classes of photopigment have been proposed: melanopsin and cryptochromes. Physiologic analysis of circadian entrainment and pupillary light responsiveness in mice lacking these proteins leads to three conclusions: (1) outer and inner retinal photoreceptors provide partially redundant information to the inner retina, (2) melanopsin is required for inner retinal phototransduction in the absence of rod and cone signaling, and (3) cryptochromes contribute to the amplitude of inner retinal phototransduction but are not strictly required. Copyright 2005, Elsevier Inc. All rights reserved.
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