# Development of Two Novel AMD Models for Evaluation of RPE Protection by the Novel Antioxidant D-DHA

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $443,342

## Abstract

PROJECT SUMMARY
Geographic atrophy (GA) is the advanced form of dry age-related macular degeneration.
Recently, anti-complement drugs have shown moderate efficacy in slowing disease
progression. The long-term goals of the proposed studies are to develop two new mouse
models of GA based on RPE oxidative stress for testing potential novel therapeutics. We will
test one such therapeutic, oral deuterated docosahexanoic acid (D-DHA), which has shown
considerable promise in an acute model of photoreceptor oxidative stress caused by intravitreal
iron injection. Oxidation of DHA has been implicated in AMD pathogenesis by Joe Hollyfield's
lab. Now it is important to determine whether this oxidation-resistant form of DHA can protect
the RPE from GA formation and expansion. The approach is to study RPE-specific glutathione
peroxidase 4 knockout mice, as well as mice given a low dose of sodium iodate, which causes
an expanding patch of GA in the superior retina. The degeneration will be characterized using in
vivo imaging (cSLO and OCT), ERG, and, after euthanasia, mass spectrometry, histology, IHC,
and qPCR. The impact will be to generate new GA models and to assess the potential of a
promising new oral drug for prevention or treatment of AMD.

## Key facts

- **NIH application ID:** 10908085
- **Project number:** 1R01EY036292-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** JOSHUA L DUNAIEF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $443,342
- **Award type:** 1
- **Project period:** 2024-09-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908085

## Citation

> US National Institutes of Health, RePORTER application 10908085, Development of Two Novel AMD Models for Evaluation of RPE Protection by the Novel Antioxidant D-DHA (1R01EY036292-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10908085. Licensed CC0.

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