Melanopsin phototransduction: beyond canonical cascades

Melanopsin is a visual pigment that is expressed in a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs). It is involved in regulating non-image forming visual behaviors, such as circadian photoentrainment and the pupillary light reflex, while also playing a role in many aspects of image-forming vision, such as contrast sensitivity. Melanopsin was initially discovered in the melanophores of the skin of the frog Xenopus, and subsequently found in a subset of ganglion cells in rat, mouse and primate retinas. ipRGCs were initially thought to be a single retinal ganglion cell population, and melanopsin was thought to activate a single, invertebrate-like Gq/transient receptor potential canonical (TRPC)-based phototransduction cascade within these cells. However, in the 20 years since the discovery of melanopsin, our knowledge of this visual pigment and ipRGCs has expanded dramatically. Six ipRGC subtypes have now been identified in the mouse, each with unique morphological, physiological and functional properties. Multiple subtypes have also been identified in other species, suggesting that this cell type diversity is a general feature of the ipRGC system. This diversity has led to a renewed interest in melanopsin phototransduction that may not follow the canonical Gq/TRPC cascade in the mouse or in the plethora of other organisms that express the melanopsin photopigment. In this Review, we discuss recent findings and discoveries that have challenged the prevailing view of melanopsin phototransduction as a single pathway that influences solely non-image forming functions.