Aberrant ocular angiogenesis underlies catastrophic loss vision due to multiple conditions including neovascular age-related macular degeneration (nvAMD), proliferative diabetic retinopathy (DR), retinopathy of prematurity (ROP), and ischemic retinal vein occlusion. Although anti-VEGF therapy has revolutionized the management of such disorders, the drugs suffer from several roadblocks. Prolonged anti-VEGF therapies are accompanied by serious risks and significant number of patients still experience vision loss despite treatment. Therefore, new insights into molecular mechanisms that promote angiogenesis in the retina are needed for the development of more effective therapies. Recent studies in the laboratory have identified a proangiogenic activity of telomerase in mouse model of experimental choroid neovascularization (CNV). Studies proposed here will build on these exciting new findings to test the hypothesis that telomerase is an important mediator of aberrant ocular angiogenesis. To this end, employing mouse model of laser injury-induced choroidal neovascularization, we will rigorously define proangiogenic activity of telomerase and examine whether and how the proangiogenic mechanisms of telomerase and VEGF signaling converge and interface. Overall, we anticipate that this study will not only provide new insights into the role of telomerase in ocular angiogenesis, but also usher in new avenues of research for examining the synergy between telomerase biology ocular angiogenesis and retinal vasculopathies in the context multiple blinding diseases.

Public Health Relevance

Abnormal growth of blood vasculature in the eye is the cause of a number of blinding eye diseases such as age-related macular degeneration, diabetic retinopathy, retinopathy of premature and neovascular glaucoma. Our proposed research will help gain a deeper understanding of the molecular mechanisms of abnormal growth of blood vessels in the eye. Findings from these studies are likely to provide insights for developing new therapies for variety of blinding diseases.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21EY030651-01
Application #
9808042
Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Shen, Grace L
Project Start
2019-09-01
Project End
2021-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
1
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Virginia
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904