Pathologic angiogenesis can cause blindness in numerous diseases of the eye including age-related macular degeneration (AMD) and diabetic retinopathy, and promote disease progression in several cancers. Although vascular endothelial cell- derived growth factor (VEGF) is critical to this process, therapies targeting VEGF have been unable to prevent abnormal blood vessel development and may be ineffective in a subset of patients, implicating other factors in the pathophysiology of disease. As such, it is critical t identify novel factors that may play a role early in disease and that are potentially independent of VEGF. We have recently identified the fibroblast growth factor (FGF) receptor signaling pathway as one that promotes choroidal neovascularization (CNV) in AMD. The mechanisms by which this occurs are novel and VEGF-independent. In these studies, we propose to identify the FGF ligands that drive pathogenic ocular neovascularization. Molecules identified by these studies are therapeutically accessible, potentially modifiable and might facilitate the development of targeted therapies to prevent blindness from complications of ocular neovascularization.

Public Health Relevance

Pathologic angiogenesis can cause blindness in diverse diseases of the eye including age-related macular degeneration and diabetic retinopathy. Although vascular endothelial cell-derived growth factor is important in ocular neovascularization, therapeutic strategies aimed at blocking this factor have been unsuccessful at preventing neovascularization. As such, it is critical to identify novel molecular pathways that promote angiogenesis in eye disease. The current proposal will focus on the role of fibroblast growth factors that promote proliferative neovascularization in the eye.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EY026707-01
Application #
9088858
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Shen, Grace L
Project Start
2016-03-01
Project End
2018-02-28
Budget Start
2016-03-01
Budget End
2017-02-28
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Washington University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130