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Abstract

Grant Number:	3R01EY000667-33S109
Project Title:	Metabolic Modulation of Vision

PI Information:	Name	Email	Title
	BARLOW, ROBERT B.	barlowr@upstate.edu	PROFESSOR

Abstract: DESCRIPTION (provided by applicant): Metabolic stress appears to be a factor in late-onset retinal degeneration in transgenic mice. We discovered retinal degeneration and loss of vision in mice rendered chronically hypoglycemic from a null mutation of the glucagon receptor gene, Gcgr, or of the prohormone convertase 2 gene, PC2. Gcgr-/- and PC2-/- mice show the first signs of degeneration and loss of acuity at about 10 months of age and become functionally blind by about 14 months. The underlying molecular and cellular mechanisms are not known, but the availability of glucose appears to be critical. Specific aims are to investigate: Aim 1: Late onset retinal degeneration in hypoglycemic mice. Aim 2: Cellular and molecular mechanisms underlying late-onset retinal degeneration. Aim 1 proposes a rigorous, systematic study of the following properties of Gcgr and PC2 null mice: retinal/RPE anatomy, retinal and photoreceptor sensitivity, retinal cell distribution and cell death, and visual function. We will track retinal degeneration in living mice using new, innovative methods: optical coherence tomography (OCT) to image retinal structures with 3.5 (m resolution and behavioral methods to measure visual function. Aim 2 proposes to test for changes in cytosolic/organellar pH from the downregulation of V-ATPase in Gcgr-/- mice. Aim 2 will also test the sensitivity of retinas to the combined stress of hypoglycemia and hypothermia, and test the efficacy of supplemental diets and antioxidants in rescuing vision of Gcgr-/- and PC2-/- mice. Potential medical benefits: (1) identification of metabolic stress as a factor in late-onset retinal degeneration, (2) development of a transgenic mouse model for retinal degeneration resulting from the null mutation of a gene, Gcgr, not expressed in the retina, (3) use of innovative methods for noninvasive measures of the retina and vision in mice, and (4) potential for yielding insights about causes of late-onset retinal degeneration in humans.

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Institution:	UPSTATE MEDICAL UNIVERSITY
	Research Administration
	SYRACUSE, NY 13210
Fiscal Year:	2009
Department:	OPHTHALMOLOGY
Project Start:	01-DEC-1977
Project End:	30-APR-2009
ICD:	NATIONAL EYE INSTITUTE
IRG:	BDPE

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