Acute photoreceptor degeneration down-regulates melanopsin expression in adult rat retina

Melanopsin in retinal ganglion cells plays an important role in mammalian circadian systems. Previous studies indicate melanopsin is responsible for circadian photoentrainment independent of classical rods and cones. However, expression of melanopsin in ganglion cells may be regulated by photoreceptors. In this study, we investigated the effects of N-methyl-N-nitrosourea (MNU)-induced acute photoreceptor degeneration on melanopsin mRNA expression and protein distribution in adult rats. Expression of melanopsin was analyzed 0.5, 1, 5, 7, 13 and 28 days after MNU administration by real-time RT-PCR and immunohistochemistry. MNU-induced gradual degeneration of photoreceptors, and by day 7 most of the photoreceptors were lost. The number of ganglion cells did not change significantly at all time points after MNU injection. In contrast, melanopsin mRNA decreased gradually with the loss of photoreceptors, at the same time pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA levels, which co-express with melanopsin in ganglion cells, were not affected by MNU treatment, indicating decrease of melanopsin mRNA levels is not due to ganglion cell damage. Distribution of melanopsin protein in the dendrites of ganglion cells dramatically decreased with the degeneration of photoreceptors, but its expression in the soma persisted for a long time. Our results suggest that intact photoreceptors maintain the expression of melanopsin and its distribution in ganglion cell dendrites.