melanopsin

Melanopsin is a photopigment expressed in a subset of retinal ganglion cells known as intrinsically photosensitive retinal ganglion cells (ipRGCs). Encoded by the OPN4 gene, melanopsin enables these cells to respond to light independently of the classical rods and cones. It was identified in the late 1990s, and the OPN4 gene encodes the protein that forms the photopigment used in non-image-forming light detection.

Melanopsin is a G-protein coupled receptor that, upon blue light stimulation, activates a Gq/11 signaling cascade. This leads to phospholipase C activation, production of IP3 and DAG, calcium release, and sustained cellular depolarization. The spectral sensitivity of melanopsin peaks in the blue range, around 460–480 nm, making ipRGC signaling particularly responsive to short-wavelength light. Although less sensitive than rods and cones, melanopsin provides a reliable signal for ambient light levels and helps sustain responses over prolonged illumination.

ipRGCs comprise several subtypes (commonly labeled M1 through M6 in mammals). M1 cells largely project to the suprachiasmatic nucleus (SCN), the brain’s central circadian clock, and drive circadian entrainment and melatonin suppression. Other ipRGC subtypes project to the olivary pretectal nucleus (OPN) and related pathways to regulate the pupil light reflex, as well as to regions involved in alertness, mood, and behavior.

Functions of melanopsin-mediated signaling include regulation of circadian rhythms, pupillary constriction to bright light, sleep-wake timing, and adaptation to daily lighting environments. Clinically, disruptions in this system can affect sleep and circadian health, and light therapy often targets melanopsin pathways to adjust circadian phase.