# Erythropoietin-mediated antioxidant pathways in glaucoma

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $57,835

## Abstract

This study will test the central hypothesis that our patented, minimally erythropoietic, form of
erythropoietin (EPO), EPO-R76E, protects retinal ganglion cells (RGCs) from glaucoma pathogenesis by
directly activating the Nrf2 pathway in these cells. Oxidative stress is known to contribute significantly to
glaucoma pathogenesis. EPO can decrease oxidative stress through activation of Nrf2 signaling to result in
increased expression of antioxidant proteins from the antioxidant response element (ARE). We will test our
hypothesis through the following Specific Aims: 1) Determine how EPO-R76E influences the Nrf2 signaling
pathway; 2) Compare EPO-R76E-induced Nrf2 pathway activation in RGCs, astrocytes, and Müller cells; and
3) Measure EPO-R76E induced signaling and the efficacy of EPO-R76E microparticles in a non-human
primate model of glaucoma. We will use the microbead occlusion model of glaucoma in both species. We will
utilize genetic and pharmacological approaches to determine the pathways activated and the relative
contributions of astrocytes, Müller cells, and RGCs in EPO-R76E induced Nrf2/ARE activation. We will use
cell-type specific recombinant adeno-associated viruses and promoters, pathway inhibitors, flow cytometry,
and microscopy. Finally, we will test the efficacy of inherently-antioxidant microparticle loaded with EPO-R76E
in a clinically relevant species, the squirrel monkey. We expect to gain greater insight into glaucoma
pathogenesis leading to the identification of druggable targets. Further, we expect to demonstrate that EPO-
R76E microparticles are a safe and effective IOP-independent treatment for glaucoma.!

## Key facts

- **NIH application ID:** 10414846
- **Project number:** 3R01EY022349-11S1
- **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:** $57,835
- **Award type:** 3
- **Project period:** 2012-04-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10414846

## Citation

> US National Institutes of Health, RePORTER application 10414846, Erythropoietin-mediated antioxidant pathways in glaucoma (3R01EY022349-11S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10414846. Licensed CC0.

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