Light Detection in the Eye – The Big Picture
Light Detection in the Eye – The Big Picture
Professor King-Wai Yau, Johns Hopkins University, USA
For well over 100 years, it has been thought that light entering the eye is absorbed only by the rod and cone photoreceptors for visual functions, triggering neural signals that propagate through the retinal neural circuitry to the ganglion cells, then to the brain via the ganglion-cell axons forming the optic nerve. About 14 years ago, however, it became clear that certain retinal ganglion cells are in fact intrinsically-photosensitive due to their expression of a visual pigment, melanopsin. In other words, they are bona fide photoreceptors. Unlike rods and cones, which partake in both image-forming and non-image-forming vision, the melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) nonetheless mediate primarily non-image-forming vision by projecting mostly to non-image-forming visual centers in the brain, such as the suprachiasmatic nucleus (for circadian photoentrainment) and the olivary pretectal nucleus (for pupillary light reflex). The ipRGCs have a low pigment content compared to rods and cones. On the other hand, they signal light as efficiently as rods, being capable of sending single-photon signals to the brain. Besides the retina, melanopsin appears to be also expressed in the iris sphincter muscle, where it activates a local pupillary light reflex independent of the canonical light-reflex circuitry through the brain. Besides rod pigment (rhodopsin), multiple cone pigments and melanopsin, it now appears that additional opsin proteins are present in the eye. In particular, an opsin called neuropsin is present in some retinal ganglion cells and uniquely mediate the photoentrainment of the retinal circadian rhythm. Neuropsin also photoentrains the rhythm of the cornea, and likely other locations in the eye as well. It is intriguing why Nature selects neuropsin instead of the other more familiar opsins for this function in the eye.
Biography of Professor King-Wai Yau, PhD
King-Wai Yau was born in China and grew up in Hong Kong. After high school and a year of medical school in Hong Kong University, he came to the US and received an A.B. in physics from Princeton (1971, University Scholar; Phi Beta Kappa; Sigma Xi) and a Ph.D. in neurobiology from Harvard (1975) under John Nicholls. He did postdoctoral work with Denis Baylor at Stanford, developing the suction-pipette-recording method that revolutionized the study of retinal rods and cones, including its ability to detect a rod’s response to a single photon. He spent 1979-81 at Cambridge, England with Sir Alan Hodgkin, during which time he became intrigued by the problem of rod/cone phototransductions. In 1981, he moved to Department of Physiology and Biophysics at University of Texas Medical Branch at Galveston, where he contributed greatly to solving this problem. He rose to full professor in 1985, and, a year later, relocated to Johns Hopkins as Professor of Neuroscience and HHMI Investigator.
At Hopkins, Yau investigated rod/cone phototransductions in ever greater detail. He also expanded over time into molecular biology, olfactory transduction, ion-channel molecular physiology, and mouse genetics. In 2002, he and David Berson of Brown University discovered intrinsically-photosensitive retinal ganglion cells expressing the visual pigment, melanopsin, and mediating mostly subconscious, non-image vision. He characterized their light responses in great detail, including likewise observing their single-photon response and recently solving their phototransduction mechanism. Most recently, he discovered yet additional retinal ganglion-cell photoreceptors expressing another visual pigment, neuropsin.
Recently, Yau also solved a 50-year-old puzzle regarding the spontaneous activation of visual pigments in darkness, providing a rationale for why natural pigments and the associated color vision do not extend into infrared. Together with colleagues Jeremy Nathans and Valeria Canto Soler at Hopkins, he has been engaged in some translational work, such as discovering bestrophin being a member of a novel family of Ca2+-activated anion channels and causing human macular degeneration when mutated, and showing human stem cells developing into an entire retina in culture with sign of photosensitivity.
Yau received England’s Rank Prize in Optoelectronics (with Denis Baylor and Trevor Lamb) in 1980, Friedenwald Award from Association of Research in Vision and Ophthalmology (1993), Alcon Award in Eye Research twice (1994, 2005), Magnes Prize from Hebrew University of Jerusalem (1996), Balazs Prize (2006) and RRF Paul Kayser International Prize (2016), the latter two from International Society for Eye Research, Portugal’s António Champalimaud Vision Award (with Jeremy Nathans) in 2008, CNIB Chanchlani Global Vision Award, Canada (2012), and the tri-yearly National Academy of Sciences Alexander Hollaender Award in Biophysics (2013). Yau is a member of National Academy of Sciences and a Fellow of American Academy of Arts and Sciences.