Retinal rod and cone photoreceptor cells mediate the essential first steps in vision by signaling light intensity and its modulation. Although the initial biochemical steps that transduce light into electrical signals in the outer segments of photoreceptors are well understood, much less is known about how outer segment currents are transformed by voltage-sensitive conductances and influenced by adaptation and circadian regulation in vivo. The work proposed in this application will investigate photoreceptor physiology the living eye and the mechanisms by which photoreceptor physiology is modulated to influence visual sensitivity and kinetics, and to mitigate photoreceptor stress. Using primarily a combination of ex vivo and in vivo electrophysiological approaches, three aims will be investigated: 1. Determine the role of Kv2.1 channels in rods. 2. Define the mechanisms that constrain photoreceptor sensitivity and kinetics in vivo. 3. Determine how photoreceptor properties are modulated by the circadian clock.
This research will provide a fundamental mechanistic understanding of photoreceptor function in the context of the living eye, and as such addresses several of the objectives recommended by the Retinal Diseases Panel (http://www.nei.nih.gov/strategicplanning/np_retinal.asp#obj), which include investigating the ?mechanisms underlying light adaptation and recovery? and the ?effects of a circadian clock in photoreceptors? [which] may present risk factors for AMD and other retinal disorders.? Finally, this work applies non-invasive technologies for assessing photoreceptor function in vivo in order to better understand normal photoreceptor function and the progressive changes that occur during disease.
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| 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 |
| Burns, Marie E; Levine, Emily S; Miller, Eric B et al. (2016) New Developments in Murine Imaging for Assessing Photoreceptor Degeneration In Vivo. Adv Exp Med Biol 854:269-75 |
| 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 |
| Fortenbach, Christopher R; Kessler, Christopher; Peinado Allina, Gabriel et al. (2015) Speeding rod recovery improves temporal resolution in the retina. Vision Res 110:57-67 |
| Gross, Owen P; Pugh Jr, Edward N; Burns, Marie E (2015) cGMP in mouse rods: the spatiotemporal dynamics underlying single photon responses. Front Mol Neurosci 8:6 |
| 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 |
| Kessler, Christopher; Tillman, Megan; Burns, Marie E et al. (2014) Rhodopsin in the rod surface membrane regenerates more rapidly than bulk rhodopsin in the disc membranes in vivo. J Physiol 592:2785-97 |
| Levine, Emily S; Zam, Azhar; Zhang, Pengfei et al. (2014) Rapid light-induced activation of retinal microglia in mice lacking Arrestin-1. Vision Res 102:71-9 |
| Arshavsky, Vadim Y; Burns, Marie E (2014) Current understanding of signal amplification in phototransduction. Cell Logist 4:e29390 |
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