Melanopsin Bistability: A Fly's Eye Technology in the Human Retina

Abstract

In addition to rods and cones, the human retina contains light-sensitive ganglion cells that express melanopsin, a photopigment with signal transduction mechanisms similar to that of invertebrate rhabdomeric photopigments (IRP). Like fly rhodopsins, melanopsin acts as a dual-state photosensitive flip-flop in which light drives both phototransduction responses and chromophore photoregeneration that bestows independence from the retinoid cycle required by rods and cones to regenerate photoresponsiveness following bleaching by light. To explore the hypothesis that melanopsin in humans expresses the properties of a bistable photopigment in vivo we used the pupillary light reflex (PLR) as a tool but with methods designed to study invertebrate photoreceptors. We show that the pupil only attains a fully stabilized state of constriction after several minutes of light exposure, a feature that is consistent with typical IRP photoequilibrium spectra. We further demonstrate that previous exposure to long wavelength light increases, while short wavelength light decreases the amplitude of pupil constriction, a fundamental property of IRP difference spectra. Modelling these responses to invertebrate photopigment templates yields two putative spectra for the underlying R and M photopigment states with peaks at 481 nm and 587 nm respectively. Furthermore, this bistable mechanism may confer a novel form of “photic memory” since information of prior light conditions is retained and shapes subsequent responses to light. These results suggest that the human retina exploits fly-like photoreceptive mechanisms that are potentially important for the modulation of non-visual responses to light and highlights the ubiquitous nature of photoswitchable photosensors across living organisms.

Effects of Artificial Dawn on Subjective Ratings of Sleep Inertia and Dim Light Melatonin Onset

“…Under broadband natural or artificial light exposure, these two states exist in equilibrium. However, under monochromatic light exposure, it was shown that whereas especially short wavelengths initiated the phototransduction cascade (from R to M), long wavelengths could restore responsiveness by regeneration of the M to the R states (Melyan et al, 2005;Mure et al, 2009). The light intensities used in Mure et al's study to drive the M state back to the R state were quite high.…”

Photic memory for executive brain responses

“…In contrast, melanopsin is a dual-state photopigment, in which photons drive both processes of phototransduction and part of chromophore regeneration (10)(11)(12). Recent rodent and human data suggest that exposure to longer wavelength light (590-620 nm; orange-red) triggers melanopsin chromophore regeneration and increases overall subsequent intrinsic photosensitivity of ipRGCs (13,14). Conversely, exposure to shorter wavelength light (∼480 nm; blue) favors phototransduction and decreases overall subsequent ipRGCs intrinsic photosensitivity (13,14).…”

“…Recent rodent and human data suggest that exposure to longer wavelength light (590-620 nm; orange-red) triggers melanopsin chromophore regeneration and increases overall subsequent intrinsic photosensitivity of ipRGCs (13,14). Conversely, exposure to shorter wavelength light (∼480 nm; blue) favors phototransduction and decreases overall subsequent ipRGCs intrinsic photosensitivity (13,14). At the physiological level (12), the existence of two stable photon absorption states allows photoconversion of melanopsin between the 11-cis and all-trans isoforms of the photopigment-bound chromophore to drive both photic responses and restoration of light responsiveness (12,14), similar to processes of invertebrate rhabdomeric photopigments (15).…”

Comparison of the isomerization mechanisms of human melanopsin and invertebrate and vertebrate rhodopsins

“…Light-induced (i.e., photochemical) isomerization of PSB11 to its all-trans isomer (PSBAT) triggers an opsin conformational change that, ultimately, activates the receptor and signaling cascade (8,9). However, similar to invertebrate and in contrast to vertebrate rhodopsins, melanopsins are bistable (10). Indeed, although vertebrate rhodopsins need a retinoid cycle (11) to regenerate PSB11, melanopsins have an intrinsic light-driven chromophore regeneration function via PSBAT back-isomerization.…”