# Elucidating the mechanism of erythropoietin (EPO) in mitigating Dry-AMD pathophysiology

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2023 · $412,738

## Abstract

PROJECT SUMMARY
Age-related macular degeneration (AMD) is one of the leading causes of irreversible visual dysfunction in older
individuals in developed countries, resulting in loss of productivity, independence, and quality of life, as well as
tremendous healthcare and economic burden. Visual dysfunction in AMD patients could be in the form of ‘‘dry’’
AMD or ‘‘wet’’ AMD or both. While some treatments are available for wet-AMD, but there is no effective treatment
for geographic atrophy (GA), the advanced form of dry-AMD. Oxidative stress-induced cellular changes play a
significant role in the loss of macular RPE and photoreceptors in dry-AMD. Treatments involving local and
sustained delivery of molecules or genes to counteract oxidative stress-induced cellular changes could prevent
RPE atrophy. Systemic or retinal delivery EPO-R76E, a modified form of EPO (with reduced erythropoietic
activity) improved the function of ganglion cells and photoreceptors cells in the retina. Because of its effect in
preventing cell death due to induction oxidative stress, we are especially interested in investigating the precise
mechanism(s) of how RPE specific EPO-R76E interacts with other retinal cells and influences aberrant molecular
pathways in controlling dry-AMD phenotype. We will interrogate the impact of EPO-R76E using two different
animal models showing AMD pathology; one is associated with induction of RPE oxidative stress, and the other
due to complement dysregulation. We will use recombinant adeno-associated virus (AAV) with serotype 1 to
achieve sustained expression of EPO-R76E and deliver to mice eye via subretinal injection. Our first aim will test
molecular mechanisms of the retinal protection by EPO-R76E using proteomics analyses of pathways and cell-
specific transcriptional approaches in a mouse model of dry-AMD. Our second aim will test whether sustained
expression of EPO-R76E ameliorates dry AMD phenotypes in animal models and interrogate how late in the
course of retinal degeneration EPO-R76E will be effective in preventing disease symptoms. Our research will
elucidate the role of EPO signaling in RPE function, retinal health, and the approach for preventive or therapeutic
intervention of dry-AMD. These studies will identify novel molecular pathways for manipulating the retina and
provide a new direction for managing dry-AMD.

## Key facts

- **NIH application ID:** 10694030
- **Project number:** 5R01EY033415-02
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Manas R Biswal
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $412,738
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10694030

## Citation

> US National Institutes of Health, RePORTER application 10694030, Elucidating the mechanism of erythropoietin (EPO) in mitigating Dry-AMD pathophysiology (5R01EY033415-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10694030. Licensed CC0.

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