# Homeostasis of the Retinal Epigenome

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $388,750

## Abstract

PROJECT SUMMARY / ABSTRACT
DNA encodes all of the information required to generate and maintain each cell within the body. However, DNA
alone is not sufficient and requires the genome to be labeled as active or inactive in a process termed epigenetics
by modifications to DNA itself or to histones around which all DNA is wrapped. These epigenetic modifications
are well established regulators of cellular development and differentiation, and their function is essential for
proper retinal development. While modifications to histone tails such as acetylation and methylation have been
extensively studied, we have not yet explored the roles of histone variants in the retina. In fact, histone H3 has
two isoforms H3.1/2 and H3.3, which are incorporated in a cellular replication dependent and independent
manner respectively. Recent evidence has emerged that mutations within H3.3 cause syndromic disorders,
which include severe neurodevelopmental issues, including in some cases retina degeneration and vision loss.
In this proposal, we aim to investigate the role of H3.3 in retinal cell fate specification and differentiation. We
have preliminary evidence that a mouse model lacking H3.3 in the developing eye causes loss of a subset of
retinal cell types. Additional data suggests H3.3 deposition is tightly regulated early in development to control
expression of an essential subset of genes. Therefore, in Aim 1 we will complete a full phenotypic
characterization of retinal development upon loss of H3.3 from retinal progenitors and post-mitotic neurons. In
Aim 2, we will investigate the molecular role of H3.3 in the establishment of the mature retinal epigenome. The
results of this study will deliver the first in depth investigation of retinal phenotype after depletion of H3.3 and
define the role of H3.3 in retinal epigenetic remodeling and homeostasis. A better understanding of the role of
H3.3 in the retina is essential to better understand retinal development and for the design of treatment paradigms
for patients with H3.3 mutations.

## Key facts

- **NIH application ID:** 10938189
- **Project number:** 1R01EY036368-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Philip Andrew Ruzycki
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $388,750
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938189

## Citation

> US National Institutes of Health, RePORTER application 10938189, Homeostasis of the Retinal Epigenome (1R01EY036368-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10938189. Licensed CC0.

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