Expression of the candidate circadian photopigment melanopsin (Opn4) in the mouse retinal pigment epithelium.

A number of responses to light, including circadian entrainment and pupillary constriction, are preserved in mammals that lack rod and cone photoreceptors. Recent studies have demonstrated that a subset of retinal ganglion cells (RGCs) are intrinsically photosensitive, and that these RGCs project to regions of the brain associated with the regulation of the circadian clock and pupil constriction. The photopigment gene(s) that mediate these effects of irradiance remain unidentified, although melanopsin (Opn4) has emerged as a strong candidate. For example, Opn4 is expressed within intrinsically photosensitive RGCs, and Opn4 knock-out mice show attenuated circadian and pupillary responses to light. In this study we provide the first clear evidence that Opn4 expression is not confined to these photosensitive RGCs, but is also expressed in the retinal pigment epithelium (RPE), a tissue with no known photosensensory role. We can preclude retinal contamination of RPE extracts as levels of Opn4 expression were higher in the RPE than in the retina, and the expression of rod opsin and Thy1 (a marker of the RGC layer) were barely detectable in RPE extracts. Our results raise questions about the presumed function of melanopsin, and highlight the need for biochemical studies on this protein.