This project will focus on mechanisms which regulate the sensitivity of vertebrate retinal rods and cones. Electrophysiological recordings of membrane current, microspectrophotometric measurements of visual pigment and fluorometric determinations of cytosolic calcium ([Ca2+]i) will be obtained from solitary rods and cones in which retinal and its analogs have been incorporated in darkness and following bright light (bleaching) to determine how cytosolic messenger substances are regulated during dark-adaptation. Three general questions will be addressed: (1) what the nature of the opsin-retinoid interaction is during dark- and bleaching-adaptation: the minimum structural interactions of opsin and retinal required for recovery of sensitivity during dark-adaptation will be determined; PDE and guanylyl cyclase velocities will be estimated in cells which have been bleached and treated with 11-cis retinal and analogs; and 13-demethyl retinal and 10-demethyl retinal will be incorporated into bleached rods and cones to test the importance of torsion in the C-11:C-12 bond in retinal during dark-adaptation; (2) what the involvement of [Ca2+]i is in light adaptation and pigment regeneration: changes in cytosolic calcium and membrane current will be measured in solitary dark-adapted and bleach-adapted rods and cones in the presence and absence of retinal and its analogs in order to determine the relationship between recovery of sensitivity during dark-adaptation and levels of [Ca2+]i; 9-demethyl retinal will be incorporated into bleached photoreceptors in order to determine whether an early phase of adaptation is due to rhodopsin turn-off since 9-demethyl rhodopsin is thought to exhibit an abnormally prolonged activated lifetime; whether or not this prolonged lifetime is modified by changes in [Ca2+]i will be determined; and (3) whether all-trans retinal occupancy of the opsin binding site is required for opsin adaptation. This latter question will be addressed by measuring sensitivity and estimating PDE and cyclase velocities in bleached rods and cones in the presence and absence of agents which are known to leach all-trans retinal/retinol from the intact photoreceptors.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY001157-27
Application #
6178376
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Mariani, Andrew P
Project Start
1977-04-01
Project End
2002-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
27
Fiscal Year
2000
Total Cost
$361,914
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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