# A new class of wet AMD therapeutics

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2024 · $377,500

## Abstract

ABSTRACT
Advanced neovascular age-related macular degeneration (AMD) is characterized by choroidal
neovascularization (CNV), in which neovessels originating from the choroid invade the macula. CNV causes
permanent central blindness if left untreated and is the most sight-threatening pathology of AMD. The present
application will investigate the efficacy and regulatory mechanisms for a new class of CNV therapeutics. We
have identified in our preliminary data that ketone bodies suppress CNV and hypothesize that this effect is
regulated by macrophage and/or microglia reprogramming, which results in protective inflammation and/or
suppression of pathological inflammation. We will refute or validate this hypothesis in three Specific Aims. In
Aim 1, we will determine the therapeutic effects of ketone metabolites and their potential synergistic effect with
anti-VEGF therapies, the current standard of care for CNV. We will also determine whether the anti-angiogenic
effects of ketone metabolites are regulated by direct effects on endothelial cells or ketone-induced immune cell
phenotypic changes using co-culture models. In Aim 2, we will identify whether ketone bodies suppress CNV
via microglia, macrophages recruited from the circulation, or both. In Aim 3, we will determine the role of the
ketone body receptor, G Protein-coupled receptor 109a (Gpr109a) in phenotypic reprogramming of specific
immune cell subpopulations.

## Key facts

- **NIH application ID:** 11142093
- **Project number:** 7R01EY034247-02
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Elizabeth Pearsall
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $377,500
- **Award type:** 7
- **Project period:** 2023-09-30 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11142093

## Citation

> US National Institutes of Health, RePORTER application 11142093, A new class of wet AMD therapeutics (7R01EY034247-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11142093. Licensed CC0.

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