# Mechanisms of Retinal Neuronal Injury

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $395,000

## Abstract

SUMMARY
Retinal neuronal death causes vision loss and blindness. Yet there is no therapy available to effectively protect
retinal neurons. This application proposes continuation of a project designed to elucidate common
mechanisms that control retinal neuronal injury in retinopathy. During the previous funding period, we
demonstrated that endoplasmic reticulum (ER) stress-induced CXL10/CXCR3 axis has a key role in retinal
inflammation, oxidative stress and neuronal injury. Our data suggest a model in which injured or stressed
retinal neurons (e.g. retinal ganglion cells (RGCs)) release CXCL10 that directly induces RGC death by
activating the cAMP/Epac1 pathway and indirectly causes RGC damage by recruiting and activating
leukocytes from blood. Epacs (Epac1 and Epac2) are novel mediators of cAMP. We now propose to determine
the central role of Epac1 in linking multiple insults in ischemic retinopathy to neuronal injury and further
investigate the interactions between neurons and vessels. Our hypothesis is that Epac1 activation plays a
causal role in retinal neuronal and vascular injury in ischemic retinopathy and pharmacologic inhibition of Epac
provides a novel therapeutic intervention for ischemic retinopathy. This application will, for the first time, use
Epac1 global KO mice, Epac1 conditional KO mice, AAV2-mediated gene delivery, novel Epac inhibitor, non-
invasive advanced imaging and functional testing to investigate the cAMP/Epac1 pathway in retinal neuronal
and vascular injury in mouse models of acute and chronic ischemic retinopathy. It will also investigate potential
mechanisms of Epac1-induced retinal neuronal damage and subsequent vascular alterations. The research is
expected to significantly advance the mechanistic understanding of ischemic retinopathy and should facilitate
the development of novel strategies to protect retinal neurons and vessels in ischemic retinopathy. This
proposal directly addresses vision research priorities identified in the NEI Publication, “Vision Research:
Needs, Gaps, & Opportunities”: 1) Apply molecular biology techniques to RGC neuroscience to dissect factors
important for survival, axon regeneration, and physiology. 2) Explore neuroprotection as an approach for
prolonging RGC function and survival.

## Key facts

- **NIH application ID:** 9961600
- **Project number:** 5R01EY022694-08
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Wenbo Zhang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $395,000
- **Award type:** 5
- **Project period:** 2012-09-30 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9961600

## Citation

> US National Institutes of Health, RePORTER application 9961600, Mechanisms of Retinal Neuronal Injury (5R01EY022694-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9961600. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*