Disease relevance of OPN4

• Here we show an anatomically distinct population of 'giant', melanopsin-expressing ganglion cells in the primate retina that, in addition to being intrinsically photosensitive, are strongly activated by rods and cones, and display a rare, S-Off, (L + M)-On type of colour-opponent receptive field [1].
• While considerable attention has been paid to the role of melanopsin in the generation of intrinsic light sensitivity in the retinal ganglion cells of mammals, nothing is known about the photoreceptive capacity of the horizontal cells of the fish retina in which both VA opsin and melanopsin are expressed [2].
• Furthermore, whether melanopsin expression is conserved in retinas of blind patients with severe retinal degeneration was investigated [3].
• To determine the proportion of ganglion cells afferent to the SCN that express melanopsin, ganglion cells were labeled following transsynaptic retrograde transport of a recombinant of the Bartha strain of pseudorabies virus (PRV152) constructed to express the enhanced green fluorescent protein (EGFP) [4].

High impact information on OPN4

• In mammals, including humans, the gland has lost direct photosensitivity, but responds to light via a multisynaptic pathway that includes a subset of retinal ganglion cells containing the newly discovered photopigment, melanopsin [5].
• This review discusses the signaling pathways that may underlie melanopsin-dependent phototransduction in native pRGCs, as well as the many exciting challenges ahead [6].
• VA opsin, melanopsin, and an inherent light response within retinal interneurons [2].
• PURPOSE: Melanopsin, expressed in a subset of intrinsically photosensitive ganglion cells that project to the suprachiasmatic nucleus (SCN), is involved in the photic entrainment of circadian rhythms and other non-image-forming functions (pupil light reflex, masking, acute heart rate response, and alertness) [7].
• Melanopsin is widely distributed in the retina of vertebrates and, depending on the species, is expressed in ganglion, amacrine, horizontal, and photoreceptor cells [7].

Biological context of OPN4

• Thus, in the diurnal trichromatic primate, 'non-image-forming' and conventional 'image-forming' retinal pathways are merged, and the melanopsin-based signal might contribute to conscious visual perception [1].
• Melanopsin: a novel photopigment involved in the photoentrainment of the brain's biological clock [8]?
• The high level of identity with opsins in both the transmembrane regions, where the chromophore binding site is located, and the intracellular loops, where the G-proteins interact, suggests that both melanopsin and pinopsin should be able to generate a stable photopigment, capable of triggering a transduction cascade mediated by G-proteins [9].
• Here, we describe the discovery and functional characterisation of a new melanopsin gene in fish, bird, and amphibian genomes, demonstrating that, in fact, the vertebrates have evolved two quite separate melanopsins [10].
• On the basis of sequence similarity, chromosomal localisation, and phylogeny, we identify our new melanopsins as the true orthologs of the melanopsin gene previously described in mammals and term this grouping Opn4m [10].

Anatomical context of OPN4

• These intrinsically photosensitive retinal ganglion cells express the putative photopigment melanopsin [11].
• Here we show that heterologous expression of human melanopsin in a mouse paraneuronal cell line (Neuro-2a) is sufficient to render these cells photoreceptive [11].
• PACAP and melanopsin were colocalized in the RGCs and PACAP-containing nerve fibers, seemingly innervating the retinorecipient part of the SCN [3].
• Based on these results, it is clear that SCN-projecting RGCs can respond to light both via an intrinsic melanopsin-based signaling cascade and via a synaptic pathway driven by classical rod and/or cone photoreceptors [12].
• Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: bifurcation and melanopsin immunoreactivity [13].

Associations of OPN4 with chemical compounds

• AIM: To analyse how intraocular lens (IOL) chromophores affect retinal photoprotection and the sensitivity of scotopic vision, melanopsin photoreception, and melatonin suppression [14].
• The melanopsin photoresponse relies on the presence of cis-isoforms of retinaldehyde and is selectively sensitive to short-wavelength light [11].
• In this study, we investigated the effects of N-methyl-N-nitrosourea (MNU)-induced acute photoreceptor degeneration on melanopsin mRNA expression and protein distribution in adult rats [15].
• Yet there is a residual phase-shifting response in melanopsin knockout mice, which suggests an alternate or redundant means for light input to the SCN of the hypothalamus [16].
• They consist of melanopsin, a protein homologous to rhodopsin, with retinal as the light-sensitive prosthetic group; and cryptochromes 1 and 2, proteins combined with methenyltetrahydrofolate and flavin adenine dinucleotide, which function as blue light-sensitive photoreceptors [17].

Regulatory relationships of OPN4

• Melanopsin is expressed in PACAP-containing retinal ganglion cells of the human retinohypothalamic tract [3].

Other interactions of OPN4

• Melanopsin, melatonin suppression, and rhodopsin sensitivities are all maximal in the blue part of the spectrum [14].
• The findings indicate that PACAP is a neurotransmitter of the RHT mediating photic information to the clock, possibly via melanopsin located exclusively on the PACAP-expressing cells of the RHT [18].
• Furthermore, immunohistochemical experiments reveal that TRPC6 is expressed in many RGCs, including those that express melanopsin [19].
• Here we show, using in situ hybridization and immunohistochemistry, that melanopsin, a recently identified opsin, is expressed in retinal ganglion cells which also co-store PACAP, a neurotransmitter of the RHT [20].
• Exceptions to this are RGR-opsin and melanopsin, whose genes have very different intron insertion positions [21].

Analytical, diagnostic and therapeutic context of OPN4

• These ganglion cells express the putative photopigment melanopsin and by signalling gross changes in light intensity serve the subconscious, 'non-image-forming' functions of circadian photoentrainment and pupil constriction [1].
• Immunohistochemistry was used to determine melanopsin expression in the retinas of three donors [7].
• METHODS: In situ hybridization and immunohistochemistry was used to demonstrate melanopsin synthesis in human eyes of 17 donors and two postmortem hypothalami containing the SCN [3].
• Expression of melanopsin was analyzed 0.5, 1, 5, 7, 13 and 28 days after MNU administration by real-time RT-PCR and immunohistochemistry [15].

References