Melanopsin Expresses Bistable Properties in the Human Retina

Abstract

Purpose: : A subpopulation of retinal ganglion cells in the human retina contain the novel photopigment melanopsin that shares structural homology and signal transduction mechanisms of invertebrate rhabdomeric photopigments (IRP). When expressed in vitro, melanopsin expresses bistable properties of IRPs by which light drives both sensory phototransduction responses and chromophore photoregeneration. We explored the hypothesis that melanopsin expresses the properties of a bistable photopigment in vivo by assaying the pupillary light reflex (PLR) in humans.

Methods: : All experiments were performed in accordance with ARVO and Institutional guidelines. Twelve subjects with normal color vision participated in the study with informed written consent. The pupillary light reflex (PLR) was measured using monochromatic light stimulations to record consensual pupillary constriction responses. The pupil size was recorded from the unilluminated eye using an infrared video pupil tracking system (ViewPoint, Arrington). The steady state and post stimulus persistence PLR were analyzed following pre-exposures to adapting short and long wavelength lights.

Results: : We show that the pupil only attains a fully stabilized state of constriction after at least 30 sec of prolonged light exposure. The spectral response function of this photoequilibrium state matches that of the melanopsin-dependent post-stimulus persistence of pupil constriction and is consistent with typical IRP photoequilibrium spectra. Previous exposures to long wavelength light increases while short wavelength light decreases the amplitude of pupil constriction, a feature also consistent with difference spectra of IRPs. Modelling these responses to invertebrate photopigment templates yields two putative spectra for the underlying R and M photopigment states.

Conclusions: : The results suggest that the human retina exploits fly-like photoreceptive mechanisms that are potentially important for the modulation of pupil, circadian and other non-visual responses to light.

Keywords: retina • photoreceptors • pupillary reflex