Classical Photoreceptors RegulateMelanopsinmRNA Levels in the Rat Retina

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Abstract
Recent studies have demonstrated that melanopsin is a key photopigment in the mammalian circadian system. This novel opsin is exclusively expressed in retinal ganglion cells that are intrinsically sensitive to light, perhaps responding via a melanopsin-based signaling pathway. Previous investigations using transgenic mice have also demonstrated that ablation of the classical photoreceptors and of melanopsin prevents entrainment of several circadian rhythms, thus demonstrating that these photoreceptors are necessary and sufficient for circadian photoreception. In this study, we investigated the effect of photoreceptor degeneration onmelanopsinmRNA regulation in RCS/N-rdyrats (Royal College of Surgeons rats with a defect in the retinal dystrophy gene). We used animals at postnatal day 21 (P21), P33, P45, and P60. At P60 degeneration of the retina in RCS/N-rdyhas advanced to the point where the majority of the photoreceptors have degenerated. Our data indicate thatmelanopsinmRNA levels were rhythmic in light/dark cycle and in constant darkness in congenic controls (RCS/N-rdy+) and in RCS/N-rdyat P21 (i.e., before the degeneration of the photoreceptors). On the other hand, in RCS/N-rdyat P60,melanopsinmRNA levels were greatly reduced (pituitary adenylate cyclase-activating polypeptidemRNA (a marker for melanopsin-containing ganglion cells). Our results suggest that classical photoreceptors (rods and cones) regulate the expression ofmelanopsinmRNA in the rat. Because RCS/N-rdyrats are a model for studies on retinitis pigmentosa in human, our data may provide an important insight on melanopsin function in patients affected by retinitis pigmentosa.