Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity

TLDR

The mammalian circadian pacemaker in the SCN is photoentrained by retinal signals, and recent evidence indicates that melanopsin‑expressing retinal ganglion cells, rather than rods or cones, serve as the key photoreceptors for this entrainment. The authors cloned rat melanopsin, produced specific antibodies, and demonstrated that melanopsin localizes to the cell bodies, dendrites, and proximal axons of a subset of RGCs, while β‑galactosidase labeling in melanopsin‑heterozygous mice shows these RGC axons project to the SCN and other circadian and pupillary light reflex nuclei. Because all intrinsically photosensitive RGCs express melanopsin, the study concludes that melanopsin is the visual pigment mediating circadian clock entrainment and other non‑image‑forming visual functions.

Abstract

The primary circadian pacemaker, in the suprachiasmatic nucleus (SCN) of the mammalian brain, is photoentrained by light signals from the eyes through the retinohypothalamic tract. Retinal rod and cone cells are not required for photoentrainment. Recent evidence suggests that the entraining photoreceptors are retinal ganglion cells (RGCs) that project to the SCN. The visual pigment for this photoreceptor may be melanopsin, an opsin-like protein whose coding messenger RNA is found in a subset of mammalian RGCs. By cloning rat melanopsin and generating specific antibodies, we show that melanopsin is present in cell bodies, dendrites, and proximal axonal segments of a subset of rat RGCs. In mice heterozygous for tau-lacZ targeted to the melanopsin gene locus, β-galactosidase–positive RGC axons projected to the SCN and other brain nuclei involved in circadian photoentrainment or the pupillary light reflex. Rat RGCs that exhibited intrinsic photosensitivity invariably expressed melanopsin. Hence, melanopsin is most likely the visual pigment of phototransducing RGCs that set the circadian clock and initiate other non–image-forming visual functions.