Retinal degenerative diseases are a major cause of visual disability and blindness worldwide. Age-related macular degeneration (AMD), for example, is the leading cause of blindness in the elderly in the Western world. Current treatments do little to alter the inexorable loss of vision due to retinal degenerations. Several studies have shown that intraocular injection of factors such as brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), or basic fibroblast growth factor-2 (FGF2), slows photoreceptor cell death caused by specific mutations or exposure to constant light. However, the clinical usefulness of these findings may be limited, because rescue effects are partial and transient, and some factors appear to have unwanted side effects. Elucidation of the mechanism by which survival factors delay retinal degenerations appears necessary in order to maximize benefits and minimize side effects. Recent studies from our laboratories have suggested that CNTF, BDNF and FGF2 do not act directly on photoreceptors; rather, they appear to act indirectly through other cells, most likely M?ller cells. Based on these observations, we propose to investigate the molecular changes triggered by neurotrophic factors in M?ller cells. The studies involve the combined use of two complementary and demanding state-of-the-art techniques: the generation of cDNA from individual cells, and their analysis using custom designed retinal cDNA microarrays. We will then establish which of these changes are important for photoreceptor survival. The potential impact of the identification of these molecules is clear, since they could offer new avenues for the treatment of these devastating diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Small Research Grants (R03)
Project #
5R03EY014341-02
Application #
6734675
Study Section
Special Emphasis Panel (ZEY1-VSN (01))
Program Officer
Mariani, Andrew P
Project Start
2003-05-01
Project End
2006-03-31
Budget Start
2004-04-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$163,500
Indirect Cost
Name
Johns Hopkins University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Wahlin, Karl J; Lim, Lynette; Grice, Elizabeth A et al. (2004) A method for analysis of gene expression in isolated mouse photoreceptor and Muller cells. Mol Vis 10:366-75