Light adaptation is the ability of a photoreceptor to make biochemical adjustments that enable it to detect changes in illumination even in the presence of what would otherwise be a saturating stimulus. A cyclic GMP-mediated enzymatic pathway is used to detect light in rod and cone photoreceptors. One of the biochemical reactions that initiates light adaptation is a Ca2+-mediated feedback pathway that regulates synthesis of cyclic GMP by guanylyl cyclase.
The aims of this application are to: (i) understand at a structural level how photoreceptor membrane guanylyl cyclases are regulated by Ca2+ and Ca2+-binding proteins; (ii) understand at the molecular level how mutations in a photoreceptor guanylyl cyclase cause a dominant degenerative disease of the retina, Autosomal Dominant Cone-Rod Dystrophy; and (iii) understand at the physiological level how regulation of cyclic GMP synthesis determines how a photoreceptor adapts to light and how well it returns to the dark state following illumination. These studies will provide fundamental information about how photoreceptors detect light and they will provide insights into the molecular basis of inherited diseases of the retina.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013572-04
Application #
6843131
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Mariani, Andrew P
Project Start
2002-02-01
Project End
2007-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
4
Fiscal Year
2005
Total Cost
$375,490
Indirect Cost
Name
University of Washington
Department
Biochemistry
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Ramamurthy, Visvanathan; Niemi, Gregory A; Reh, Thomas A et al. (2004) Leber congenital amaurosis linked to AIPL1: a mouse model reveals destabilization of cGMP phosphodiesterase. Proc Natl Acad Sci U S A 101:13897-902
Ramamurthy, Visvanathan; Roberts, Melanie; van den Akker, Focco et al. (2003) AIPL1, a protein implicated in Leber's congenital amaurosis, interacts with and aids in processing of farnesylated proteins. Proc Natl Acad Sci U S A 100:12630-5