Corneal exposure to chemicals by accident (e.g. alkali burn) or during a terrorist attack against U.S. civilians or armed forces (e.g. sulfur mustard burn) often leads to corneal neovascularization that is characterized by the invasion of new blood vessels into the cornea from the limbus. Corneal neovascularization is a vision- threatening condition that may lead to lipid deposition, edema, persistent inflammation and scarring, resulting in impairment of corneal transparency and visual acuity. Currently, there are only a few options to treat corneal neovascularization and these treatments have significant limitations. There is a great need to develop new strategies and therapies to prevent corneal neovascularization and vision loss against chemical threats. In this application for Administrative Supplements, we propose to conduct experiments to generate preliminary data to determine if Epac1 also plays a role in corneal neovascularization after chemical injury. The feasibility of the work proposed is strongly supported by data generated from the research progress of the parental award and by our preliminary data. Based on pilot data from this work, in the future, we will further evaluate and optimize the therapeutic effects of ESI-09 and other novel Epac inhibitors in a rabbit model of corneal nitrogen mustard burn. The proposed pilot work, together with future studies following this work, is expected to significantly facilitate the development of novel countermeasures to treat corneal neovascularization and restore vision after chemical threats.

Public Health Relevance

Epacs (Epac1 and Epac2) are novel mediators of cAMP, one of the most common second messengers involved in pathophysiological conditions. This project is designed to understand the role of Epac1 corneal neovascularization after chemical injury.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
3R01EY026629-04S1
Application #
10177281
Study Section
Program Officer
Shen, Grace L
Project Start
2020-09-01
Project End
2021-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
4
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Texas Med Br Galveston
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
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