Human vision operates over a billion-fold range of light intensities ranging from starlight to bright daylight, with night vision subserved by retinal rod photoreceptor cells, and day vision by cone photoreceptor cells. Rods and cones mediate the first steps in vision by capturing light in their G-protein coupled receptors Rhodopsin, and L/M and S-cone opsins, respectively, whose activation then generates electrical responses through homologous G-protein-coupled receptor signaling cascades. While the molecular mechanisms that underlie the rod's ability to signal in dim light are now well understood, the mechanisms that enable some cones (but not rods) to function in bright daylight are relatively poorly understood. Using non-invasive optical and electroretinographic methodology applicable to humans, the proposed work proposed will investigate cone and rod function in vivo under daylight conditions, testing hypotheses about the mechanisms that allow cones expressing only M-opsin to operate in bright light, while cones expressing only S-opsin, and rods do not, and to understand how the very abundant, non- signaling rods cope with the enormous stress that daylight makes on their molecular machinery. Among key resources for the project are cone-monochromat mice created by the author and his collaborators, which only express one cone opsin, and adaptive-optics (AO) optical coherence tomography (OCT) and scanning laser ophthalmoscopy (SLO) customized and calibrated for precisely controlling the quantity of light captured by each of the mouse opsins. The work in this project addresses a fundamental need for in vivo studies of cone and rod function in daylight conditions, to establish cellular and molecular mechanistic foundations that support and interpret the signal advances in AO imaging of human cones and rods.
! This research will provide a fundamental mechanistic understanding of photoreceptor function in the living eye under daytime conditions, and as such addresses objectives of the Retinal Diseases Panel (https://www.nei.nih.gov/sites/default/files/nei-pdfs/VisionResearch2012.pdf), which include investigating the ?mechanisms underlying light adaptation and recovery? and ?understand(ing) the molecular mechanisms and pathways in cone photoreceptors that have not been studied as extensively as (those of) rods.? The work develops and employs non-invasive optical technologies for assessing photoreceptor function in vivo in animal models, to advance the mechanistic understanding of human photoreceptor optical imaging.
|Wang, Xinlei; Miller, Eric B; Goswami, Mayank et al. (2017) Rapid monocyte infiltration following retinal detachment is dependent on non-canonical IL6 signaling through gp130. J Neuroinflammation 14:121|
|Peinado Allina, Gabriel; Fortenbach, Christopher; Naarendorp, Franklin et al. (2017) Bright flash response recovery of mammalian rods in vivo is rate limited by RGS9. J Gen Physiol 149:443-454|
|Zhang, Pengfei; Zawadzki, Robert J; Goswami, Mayank et al. (2017) In vivo optophysiology reveals that G-protein activation triggers osmotic swelling and increased light scattering of rod photoreceptors. Proc Natl Acad Sci U S A 114:E2937-E2946|
|Lu, Chen D; Lee, ByungKun; Schottenhamml, Julia et al. (2017) Photoreceptor Layer Thickness Changes During Dark Adaptation Observed With Ultrahigh-Resolution Optical Coherence Tomography. Invest Ophthalmol Vis Sci 58:4632-4643|
|Zhang, Pengfei; Goswami, Mayank; Zawadzki, Robert J et al. (2016) The Photosensitivity of Rhodopsin Bleaching and Light-Induced Increases of Fundus Reflectance in Mice Measured In Vivo With Scanning Laser Ophthalmoscopy. Invest Ophthalmol Vis Sci 57:3650-64|
|Zhang, Pengfei; Goswami, Mayank; Zam, Azhar et al. (2015) Effect of scanning beam size on the lateral resolution of mouse retinal imaging with SLO. Opt Lett 40:5830-3|
|Bonora, Stefano; Jian, Yifan; Zhang, Pengfei et al. (2015) Wavefront correction and high-resolution in vivo OCT imaging with an objective integrated multi-actuator adaptive lens. Opt Express 23:21931-41|
|Zhang, Tao; Enemchukwu, Nduka O; Jones, Alex et al. (2015) Genetic deletion of S-opsin prevents rapid cone degeneration in a mouse model of Leber congenital amaurosis. Hum Mol Genet 24:1755-63|
|Zhang, Pengfei; Zam, Azhar; Jian, Yifan et al. (2015) In vivo wide-field multispectral scanning laser ophthalmoscopy-optical coherence tomography mouse retinal imager: longitudinal imaging of ganglion cells, microglia, and Müller glia, and mapping of the mouse retinal and choroidal vasculature. J Biomed Opt 20:126005|
|Zawadzki, Robert J; Zhang, Pengfei; Zam, Azhar et al. (2015) Adaptive-optics SLO imaging combined with widefield OCT and SLO enables precise 3D localization of fluorescent cells in the mouse retina. Biomed Opt Express 6:2191-210|
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