Light detection in the eye - The big picture
Professor of Neuroscience
Johns Hopkins University School of Medicine
In this talk, I shall broadly describe what we now know about the various ocular photoreceptor cells and their respective phototransduction mechanisms. FIRST, retinal rods and cones detect light predominantly for image-forming vision, using a cGMP signaling cascade and cyclic-nucleotide-gated (CNG) cation channels for phototransduction ("ciliary motif"). Some of our recent, still unpublished experiments indicate that the signal amplification at the rhodopsin-transducin step in rods is only ~20 transducins activated per photoismerized rhodopsin instead of being much larger. Also, we have succeeded in quantifying the spontaneous (thermal) activity of certain cone pigments besides rhodopsin, and in explaining this spontaneous activity in darkness ("dark light") for essentially all pigments based on a simple physicochemical theory; as such, we offer a rationale for why opsin-based, infrared-detecting pigments do not appear to exist in Nature. Finally, we have succeeded in quantifying the constitutive activity of bleached rhodopsin, which underlies bleaching adaptation. SECOND, a small percentage (~1-3%) of retinal ganglion cells are intrinsically photosensitive (ipRGCs), using melanopsin as the visual pigment. They are largely responsible for non-image-forming vision, although not exclusively. They comprise several subtypes, M1 through M5, being distinct from each other in morphology, response properties, and projection targets in the brain. Surprisingly, we discovered two phototransduction pathways in these cells. M1-ipRGCs use PLC-beta4 and TRPC6,7 cations channels, literally identical in mechanism to that found in fly eye ("rhabdomeric motif"). M4-ipRGCs, however, use a hitherto undescribed pathway also of the "ciliary motif" -- with cyclic nucleotide as second messenger but HCN cation channels as the terminal step to lead to membrane depolarization. Most surprisingly, M2-ipRGCs use both pathways for phototransduction in each cell. Such a dual-mehanism is unique in the animal kingdom and may offer new insight into photoreceptor evolution. FOURTH, in fish retina, we found that some horizontal cells (specifically cone-driven ones) are also intrinsically photosensitive albeit of low sensitivity. FIFTH, ocular photosensitivity also exists outside the retina. We found that practically all nocturnal/crepuscular sub-primate mammals have an intrinsically-photosensitive iris sphincter muscle, thus producing a local pupillary light reflex even in the absence of the brain's neural circuitry. This feature, however, is absent in diurnal sub-primates and nocturnal/diurnal primates. SIXTH, we have also found neuropsin, which is another opsin, both inside and outside the retina. Neuropsin appears to have a circadian-photoentrainment function in the eye.
Dr. Yau received an A.B. in physics from Princeton (1971) and a Ph.D. in neurobiology (under John Nicholls) from Harvard (1975). He did postdoctoral work with Denis Baylor at Stanford and with Alan Hodgkin at Cambridge, UK. He was on the faculty of University of Texas Medical Branch at Galveston (1980-86), becoming Professor of Physiology and Biophysics in 1985. For the past 32 years, he has been Professor of Neuroscience at Johns Hopkins University School of Medicine.