# Role of the Nrf2/ARE pathway in retinal ganglion cells during glaucoma pathogenesis and neuroprotection

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $59,624

## Abstract

Project Summary
 Glaucoma is the world's leading cause of irreversible vision loss. The only modifiable risk factor for
glaucoma is intraocular pressure (IOP) and thus all existing medical and surgical approaches target the IOP.
Unfortunately, many patients continue to lose vision despite IOP management. Glaucoma involves progressive
degeneration of retinal ganglion cells (RGCs), whose axons form the optic projection from retina to brain. Thus,
our long-term goal is to develop new treatments to abate this neurodegeneration directly in an IOP-
independent manner, based on identification and targeting of critical mechanisms of disease progression. We
previously reported that erythropoietin or a mutated version of it, EPO-R76E, are able to preserve the RGCs in
models of glaucoma. Our data shows that it modulates neuroinflammation and increases expression of
antioxidant proteins. In our parent R01, we propose to use gene therapy strategies in the microbead occlusion
model to determine the role of NRF2 and the antioxidant response element in EPO-R76E-mediated
neuroprotection in glia and RGCs, separately, in glaucoma. In this supplement application, we propose to
expand the scope of investigation to explore the endogenous response of the retina and RGCs to
hypertension-induced oxidative stress. The anticipated significant accomplishment of this proposal is
identification of new druggable targets early in glaucoma pathogenesis and clarity on the cell types to target,
which will increase the safety and efficacy of treatments. It also provides an unique opportunity for Sarah
Naguib to be mentored into an independent vision researcher poised for a successful post-doctoral fellowship.

## Key facts

- **NIH application ID:** 10291073
- **Project number:** 3R01EY022349-10S1
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** David J. Calkins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $59,624
- **Award type:** 3
- **Project period:** 2012-04-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10291073

## Citation

> US National Institutes of Health, RePORTER application 10291073, Role of the Nrf2/ARE pathway in retinal ganglion cells during glaucoma pathogenesis and neuroprotection (3R01EY022349-10S1). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/10291073. Licensed CC0.

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