More than 60% of people with Alzheimer's disease (AD) exhibit decline in visual function(s) that significantly affects life quality of AD patients. Meanwhile, poor vision also contributes to cognitive decline. Nevertheless, few studies have been done to address the needs of how to prevent or treat vision loss in AD patients. One of the major focuses in this award is to determine the pathological role of Epac1 in the injury of neurons in the inner nuclear layer (in particular bipolar cells) and photoreceptors during retinopathy of prematurity. In this application for Administrative Supplements, we propose to conduct experiments to generate preliminary data to determine if Epac1 also plays a role in the injury of bipolar cells and their connected retinal ganglion cells (RGCs) in AD. 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 determine cellular and molecular mechanisms by which Epac1 induces bipolar cell and RGC injury in AD, and investigate if pharmacologic inhibition of Epac protects vision loss in AD. Since retina and brain share many common pathophysiological mechanisms, future studies will also investigate whether Epac1 plays a role in behavioral deficits and pathological changes in the brain in AD. The proposed pilot work, together with future studies following this work, is expected to significantly advance the mechanistic understanding of retina and brain injury in AD, and should facilitate the development of novel strategies to protect neurons in AD.

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 in the injury of bipolar cells and their connected retinal ganglion cells (RGCs) in AD.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
3R01EY026629-02S1
Application #
9719041
Study Section
Program Officer
Shen, Grace L
Project Start
2017-02-01
Project End
2022-01-31
Budget Start
2018-09-30
Budget End
2019-01-31
Support Year
2
Fiscal Year
2018
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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