ipRGCs

Intrinsic photosensitive retinal ganglion cells, or ipRGCs, are a class of retinal ganglion cells that express melanopsin, enabling them to detect light independently of the classical photoreceptors, rods and cones. They constitute a minority of retinal ganglion cells in mammals and play a key role in non-image-forming visual functions such as circadian photoentrainment and the pupil light reflex, while also providing modulatory input to some image-forming pathways.

Melanopsin-based phototransduction in ipRGCs uses Gq/11 signaling, leading to phospholipase C activity and depolarization. ipRGCs produce sustained, slowly adapting responses to light and have a peak sensitivity in the blue range of the spectrum, around 470–480 nm. They can receive synaptic input from rods and cones, allowing integration of ambient light information with intrinsic signaling, which supports responses under a wide range of lighting conditions.

Anatomically, ipRGCs project to several brain regions. The primary non-image-forming pathway is the retinohypothalamic tract to the suprachiasmatic nucleus (SCN), where light information helps regulate circadian rhythms. ipRGCs also project to the olivary pretectal nucleus (OPN), which mediates the pupil light reflex, and to other regions such as the lateral geniculate nucleus and various hypothalamic and midbrain structures, contributing to mood, sleep, and alertness in response to light.

Subtypes of ipRGCs, commonly labeled M1 through M5, differ in morphology, melanopsin expression, and projection targets. In humans, M1-like and M2-like ipRGCs are well described. ipRGCs are relatively resilient to retinal degeneration and can sustain functional signaling when rods and cones are compromised, a feature that underpins therapeutic approaches using light to influence circadian and sleep processes.