This application has two parts. First, we propose to investigate the mechanisms of bleaching and dark adaptation in photoreceptors. Second, we will investigate how light regulates oxidative metabolism in rods and cones. Electrical responses of isolated cells will be measured with suction micropipettes. Substances will be introduced into isolated photoreceptors via patch pipettes. Oxygen consumption in single cells will be measured with oxygen-sensitive microelectrodes. Specifically: 1a. We shall investigate the role of G-protein activation in bleaching adaptation. Activators (GTP-gamma-s, GMP-PNP) of G-proteins will be introduced via patch pipettes into isolated cells to estimate GTP turnover in darkness, during background light, and following bleaching to investigate the notion, suggested by our preliminary data, that bleached pigment (opsin) activates transducin. 1b. We shall investigate the mechanism of the activation of transducin by bleached pigment. Previous experiments have established that bleached pigment (probably opsin) activates PDE and guanylyl cyclase in rods and cones and is probably responsible for bleaching adaptation. We will compare membrane noise which is activated by dim background light with that associated with bleaching to test whether this activation occurs via recycling of pigment intermediates to R* or activates transducin directly. 1c. We shall investigate the role of changes in [Ca2+]i during bleaching adaptation and dark adaptation. We shall make measurements of [Ca2+]i in dark adapted photoreceptors, bleached photoreceptors, and bleached photoreceptors which have been exposed to 11-cis retinal and certain of its analogues. 2. We shall begin to investigate the role that ganglion cells (and other proximal retinal neurons) play in adaptation. Previously, it has been shown that light too dim to adapt rods, adapts ganglion cells and it is thought that this occurs via synaptic interactions in the retina. We will test to see if this is true by comparing background adaptation (associated with photon noise) and bleaching adaptation (which has a much lower noise component) at the level of ganglion cells. 3. We shall investigate the mechanisms whereby light activates changes in oxygen consumption in isolated photoreceptor cells. We shall do this by simultaneously measuring single cell sensitivity and oxygen consumption during and following the release of Ca2+, ATP, and ADP from caged compounds introduced into the cell from patch pipettes.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY001157-24
Application #
2391638
Study Section
Visual Sciences C Study Section (VISC)
Project Start
1977-04-01
Project End
1998-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
24
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Boston University
Department
Physiology
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Sato, Shinya; Frederiksen, Rikard; Cornwall, M Carter et al. (2017) The retina visual cycle is driven by cis retinol oxidation in the outer segments of cones. Vis Neurosci 34:E004
Yue, Wendy Wing Sze; Frederiksen, Rikard; Ren, Xiaozhi et al. (2017) Spontaneous activation of visual pigments in relation to openness/closedness of chromophore-binding pocket. Elife 6:
Frederiksen, Rikard; Nymark, Soile; Kolesnikov, Alexander V et al. (2016) Rhodopsin kinase and arrestin binding control the decay of photoactivated rhodopsin and dark adaptation of mouse rods. J Gen Physiol 148:1-11
Berry, Justin; Frederiksen, Rikard; Yao, Yun et al. (2016) Effect of Rhodopsin Phosphorylation on Dark Adaptation in Mouse Rods. J Neurosci 36:6973-87
Toomey, Matthew B; Lind, Olle; Frederiksen, Rikard et al. (2016) Complementary shifts in photoreceptor spectral tuning unlock the full adaptive potential of ultraviolet vision in birds. Elife 5:
Wilby, David; Toomey, Matthew B; Olsson, Peter et al. (2015) Optics of cone photoreceptors in the chicken (Gallus gallus domesticus). J R Soc Interface 12:20150591
Toomey, Matthew B; Collins, Aaron M; Frederiksen, Rikard et al. (2015) A complex carotenoid palette tunes avian colour vision. J R Soc Interface 12:20150563
Wang, Jin-shan; Nymark, Soile; Frederiksen, Rikard et al. (2014) Chromophore supply rate-limits mammalian photoreceptor dark adaptation. J Neurosci 34:11212-21
Frederiksen, Rikard; Boyer, Nicholas P; Nickle, Benjamin et al. (2012) Low aqueous solubility of 11-cis-retinal limits the rate of pigment formation and dark adaptation in salamander rods. J Gen Physiol 139:493-505
Nymark, S; Frederiksen, R; Woodruff, M L et al. (2012) Bleaching of mouse rods: microspectrophotometry and suction-electrode recording. J Physiol 590:2353-64

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