Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin

作者：Yingbin Fu, Haining Zhong, Min-Hua H. Wang, Dong-Gen Luo, Hsi‐Wen Liao, Hidetaka Maeda, Samer Hattar, Laura J. Frishman, King‐Wai Yau · 发表于：Proceedings of the National Academy of Sciences · 年份：2005 · DOI：10.1073/pnas.0501866102 · 被引用次数：149 · 研究领域：Circadian rhythm and melatonin、Retinal Development and Disorders、Olfactory and Sensory Function Studies

In mammals, intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate non-image-forming visual functions such as pupillary light reflex (PLR) and circadian photoentrainment. This photosensitivity requires melanopsin, an invertebrate opsin-like protein expressed by the ipRGCs. The precise role of melanopsin remains uncertain. One suggestion has been that melanopsin may be a photoisomerase, serving to regenerate an unidentified pigment in ipRGCs. This possibility was echoed by a recent report that melanopsin is expressed also in the mouse retinal pigment epithelium (RPE), a key center for regeneration of rod and cone pigments. To address this question, we studied mice lacking RPE65, a protein essential for the regeneration of rod and cone pigments. Rpe65-/- ipRGCs were approximately 20- to 40-fold less photosensitive than normal at both single-cell and behavioral (PLR) levels but were rescued by exogenous 9-cis-retinal (an 11-cis-retinal analog), indicating the requirement of a vitamin A-based chromophore for ipRGC photosensitivity. In contrast, 9-cis-retinal was unable to restore intrinsic photosensitivity to melanopsin-ablated ipRGCs, arguing against melanopsin functioning merely in photopigment regeneration. Interestingly, exogenous all-trans-retinal was also able to rescue the low sensitivity of rpe65-/- ipRGCs, suggesting that melanopsin could be a bistable pigment. Finally, we detected no melanopsin in the RPE and no changes in rod and cone sensitivities due to...