# The Role of Histone Deacetylases in Age-related Macular Degeneration

> **NIH NIH R01** · EAST TENNESSEE STATE UNIVERSITY · 2022 · $351,564

## Abstract

Project Summary:
Most scientific understanding of epigenetic biology is in the field of development and cancer. In my early career
period, I have been investigating various pathways of pro-inflammatory signaling in the retina and have recently
discovered a powerful ability for biochemical modification of histones, a protein that complexes with DNA to
form the nucleosome, to regulate the expression of specific inflammatory factors found in AMD. The striking
changes in pro-inflammatory gene signatures that can be induced by inhibiting deacetylation of histones
suggest that this pathway may be involved in the pathogenesis of AMD. Preliminary data demonstrated
decreased expression of critical enzymes involved in these pathways in advanced dry AMD eyes and in
experimental models of oxidative stress. Inhibition of histone deacetylation resulted in significant cytotoxic
effects on the retinal pigment epithelium. In this project, I plan to rigorously dissect the role of histone
deacetylase expression and function in the pathogenesis of dry AMD and RPE cell death using a novel mouse
model and correlate in vitro studies. The proposed work will directly address a fundamental lack of knowledge
on the role of histone deacetylases in the regulation of retinal inflammation and cell death making the work
underway critically important in our search for effective targeted therapeutics for dry AMD.

## Key facts

- **NIH application ID:** 10376185
- **Project number:** 5R01EY028206-06
- **Recipient organization:** EAST TENNESSEE STATE UNIVERSITY
- **Principal Investigator:** Mark E Kleinman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $351,564
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10376185

## Citation

> US National Institutes of Health, RePORTER application 10376185, The Role of Histone Deacetylases in Age-related Macular Degeneration (5R01EY028206-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10376185. Licensed CC0.

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