Retinal and choroidal neovascularization (NV) account for a large majority of severe visual loss in developed countries each year and therefore new treatments are needed. Angiostatin and endostatin are proteolytic fragments of larger proteins that have been shown to inhibit tumor angiogenesis in mice. Pigment epithelium-derived factor (PEDF) is produced by the retinal pigmented epithelium (RPE) and other cells of the eye and inhibits corneal NV. Transforming growth factor-b I (TGFP 1) has been demonstrated to inhibit blood vessel growth in some settings. We hypothesize that expression of angiostatin, endostatin, PEDF and/or TGFP 1 in the eye will inhibit retinal and/or choroidal NV. To test this hypothesis, I will express each of these proteins in transgenic mice and compare transgene-positive mice with littermate controls in 3 models of ocular NV. I will perform similar experiments using mice that have had intraocular injection of adenovirus (AV) or adeno-associated virus (AAV) vector containing a construct for one of the 4 proteins, an approach with direct clinical application. Research training will focus on gaining a detailed understanding of the pathogenesis of ocular NV under Peter Campochiaro at the Wilmer Institute and the molecular biology of AAV under William Hauswirth at the University of Florida. Clinical training will focus on subretinal surgery utilizing techniques that will be used for gene transfer to the retina and RPE in humans. This project should provide important new information, while providing me the training necessary to become an independent investigator in the area of ocular NV utilizing a gene therapy approach. It will also provide me with clinical training to eventually translate the knowledge into new treatments for patients.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08EY013420-05
Application #
6878477
Study Section
Special Emphasis Panel (ZEY1-VSN (02))
Program Officer
Dudley, Peter A
Project Start
2001-04-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2007-03-31
Support Year
5
Fiscal Year
2005
Total Cost
$224,384
Indirect Cost
Name
Johns Hopkins University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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