Age-related macular degeneration (AMD) is the most common cause of legal blindness in the US. There is no effective treatment for the most prevalent atrophic (dry) form of AMD. The loss of vision in atrophic AMD is caused by degeneration of photoreceptor cells (rods and cones) in the central part of the retina called macula. Preservation of macular rods and cones is the ultimate goal of AMD treatment. NR2E3 is an orphan nuclear receptor expressed exclusively in photoreceptor cells of the retina where it is involved in photoreceptor maintenance and differentiation. Our overall objective is to identify a small molecule NR2E3 agonist suitable for performing proof-of-concept photoreceptor protection experiments in animal models of retinal degeneration. Identification of NR2E3 agonists will also provide an important pharmacological tool for probing basic biologic mechanisms of photoreceptor development and differentiation. The studies outlined in this proposal seek to develop an HTRF assay for agonist-induced release of corepressor NCOR from the NR2E3-NCOR complex (Specific Aim 1) and to adapt this assay to the HTS format suitable for screening of a compound collection at one of the NIH MLSCN screening centers (Specific Aim 2).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS061718-02
Application #
7501989
Study Section
Special Emphasis Panel (ZMH1-ERB-Y (06))
Program Officer
Scheideler, Mark A
Project Start
2007-09-30
Project End
2011-02-28
Budget Start
2009-03-01
Budget End
2011-02-28
Support Year
2
Fiscal Year
2009
Total Cost
$40,250
Indirect Cost
Name
Columbia University (N.Y.)
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Qin, Qiong; Knapinska, Anna; Dobri, Nicoleta et al. (2013) In pursuit of synthetic modulators for the orphan retina-specific nuclear receptor NR2E3. J Ocul Pharmacol Ther 29:298-309