Signalling by melanopsin (OPN4) expressing photosensitive retinal ganglion cells

Abstract

Over the past two decades there have been significant advances in our understanding of both the anatomy and function of the melanopsin system. It has become clear that rather than acting as a simple irradiance detector the melanopsin system is in fact far more complicated. The range of behavioural systems known to be influenced by melanopsin activity is increasing with time, and it is now clear that melanopsin contributes not only to multiple non-image forming systems but also has a role in visual pathways. How melanopsin is capable of driving so many different behaviours is unclear, but recent evidence suggests that the answer may lie in the diversity of melanopsin light responses and the functional specialisation of photosensitive retinal ganglion cell (pRGC) subtypes. In this review, we shall overview the current understanding of the melanopsin system, and evaluate the evidence for the hypothesis that individual pRGC subtypes not only perform specific roles, but are functionally specialised to do so. We conclude that while, currently, the available data somewhat support this hypothesis, we currently lack the necessary detail to fully understand how the functional diversity of pRGC subtypes correlates with different behavioural responses, and ultimately why such complexity is required within the melanopsin system. What we are lacking is a cohesive understanding of how light responses differ between the pRGC subtypes (based not only on anatomical classification but also based on their site of innervation); how these diverse light responses are generated, and most importantly how these responses relate to the physiological functions they underpin.

Unconventional Roles of Opsins

“…While rods and cones facilitate image formation, direct light sensation by ipRGCs primarily drives non-image forming functions, although, it also promotes a rudimentary form of image formation (Ecker et al 2010, Hughes et al 2016, Schmidt et al 2011). The discovery of non-image forming functions in the eye traces back to observations that blind mice can shift their circadian rhythms according to an external light-dark cycle (Foster et al 1991, Freedman et al 1999, Provencio et al 1994).…”

“…These include photoentrainment of circadian rhythms (Freedman et al 1999, Panda et al 2002), light-induced pupillary constriction (Lucas et al 2003, Xue et al 2011), suppression of pineal melatonin (Lucas et al 1999), light aversion (Johnson et al 2010, Semo et al 2010), control of sleep states (Altimus et al 2008, Hubbard et al 2013, Lupi et al 2008, Milosavljevic et al 2016, Pilorz et al 2016, Tsai et al 2009), and other functions (Atkinson et al 2013, Esquiva et al 2016, Rao et al 2013, Reifler et al 2015, Zhang et al 2008). The discoveries of melanopsin and its myriad of non-image and rudimentary image forming functions in the eye are covered in detail in other reviews (Do & Yau 2010, Hankins et al 2008, Hughes et al 2016, Lucas 2013, Matynia 2013, Schmidt et al 2011). …”

The retinal clock in mammals: role in health and disease

“…24,25 This subsequently led to the discovery of a novel opsin, melanopsin (OPN4), expressed in a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs), with a peak of sensitivity at ~480 nm. [26][27][28] It is now clear that ipRGCs combine their direct intrinsic responses with signals derived from rods and cones to regulate diverse non-image-forming responses, 29 with each photoreceptor encoding distinct parameters of the light. [30][31][32][33][34] However, we currently lack a comprehensive understanding of how light regulates the retinal clock in mammals and of the role of the different photoreceptors.…”

Research Article Analysis of melanopsin gene expression in the rabbit retina at different ages.

“…Since its discovery, the presence and activity of melanopsin have been described within the retina of at least one species of each of the group of vertebrates. Furthermore, there is an established classification of several ipRGC subtypes in mice and rats (Sand et al, 2012;Hughes et al, 2016) and in humans and macaques (Liao et al, 2016).…”