Neovascularization in the eye is a central component of many. disorders leading to severe vision impairment. Proliferative diabetic retinopathy alone is the leading cause of blindness in Americans aged 20-74. Although significant progress has been made, our ability to prevent and treat neovascular disorders would clearly benefit from a more thorough knowledge of angiogenesis at the cellular and molecular levels. The long term goal of our research program has been to understand the sequence of events that occur when normally quiescent ocular endothelial cells (EC) dedifferentiate into the proliferative, angiogenic phenotype required for new blood vessel formation. This study focuses on a set of novel genes recently identified in our laboratory that are expressed in proliferating EC. mRNAs corresponding to these genes were isolated by affinity chromatography (and subsequently cloned) using an essential RNA binding protein as bait that is itself expressed selectively in proliferating EC.
Our aims for the proposed project are to characterize these novel gene products and test whether they are essential to the angiogenic phenotype.
Specific Aim #1 is designed to tell us which are upregulated in proliferating EC, and therefore more likely to function in promoting or maintaining the angiogenic phenotype. Cultured retinal EC under quiescent and angiogenic conditions will be examined by immunochemical and hybridization techniques, as will be ocular tissues induced to undergo neovascularization in vivo.
In Aim #2, we will generate full length cDNA clones to facilitate structural analysis and development of functional probes (molecular and immunological).
In Aim #3 we will test the hypothesis that these molecules are essential for maintaining the angiogenic phenotype. This will be accomplished by introducing antagonists into cells and assessing their ability to inhibit proliferation and expression of other phenotype-specific traits. This study will add to our general knowledge of gene expression in proliferating vascular EC of the eye, but also has the potential for revealing specific regulatory points in ocular angiogenesis and other disease processes involving cell dedifferentiation and proliferation.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013176-04
Application #
6895082
Study Section
Special Emphasis Panel (ZRG1-VISC (01))
Program Officer
Dudley, Peter A
Project Start
2002-05-01
Project End
2007-04-30
Budget Start
2005-05-01
Budget End
2007-04-30
Support Year
4
Fiscal Year
2005
Total Cost
$213,000
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112