# Elucidating the role of DNA methyltransferases in epigenetic regulation of retinal regeneration in zebrafish

> **NIH NIH F30** · WAYNE STATE UNIVERSITY · 2021 · $44,030

## Abstract

Project Abstract
According to the National Eye Institute, there are currently over 12 million Americans suffering
from diseases affecting the retina. To present, therapeutic attempts to reduce retinal death or
replace lost neurons have been met with limited success, highlighting the need for an alternative
approach to this problem. The zebrafish is becoming an increasingly popular model to study
mechanisms of stem-cell based tissue regeneration. In response to extensive retinal injury,
zebrafish are able to completely regenerate the retina. This is accomplished through the induction
of Müller glial cells which undergo an asymmetric division to generate a pool of progenitor cells
that go on to regenerate all cell types of the retina with no evidence of the glial scarring observed
in mammalian species. While the remarkable capacity of the zebrafish to regenerate tissues has
been known for years, our understanding of the comparative biology between mammalian and
teleost responses to retinal damage remains poorly understood. To present, studies of retinal
regeneration in the zebrafish have largely focused on identifying signaling pathways and
individual genes involved in retinal regeneration. The epigenetic orchestration of these pathways,
however, remains to be investigated in the zebrafish. DNA methyltransferases (Dnmts) have been
studied extensively in mammals and have been identified as critical in the homeostatic
maintenance of adult stem cell processes such as hematopoietic stem cell development. The
limited literature of epigenetic regulators in zebrafish reveals that teleost species appear to utilize
the same mechanisms of epigenetic regulation as mammalian species, with zebrafish Dnmts
baring considerable sequence homology to mammalian Dnmts. It is known that immediately
following retinal injury in the zebrafish there is an initial global DNA hypomethylation and
subsequent increase in DNA methylation as the pools of progenitor cells begin to differentiate,
indicating the importance of the epigenetic landscape during these processes. With the
experiments planned in this proposal, we aim to identify the role of Dnmts in orchestrating the
process of adult retinal regeneration in the zebrafish, with the goal of elucidating pathways
regulated in Müller glial derived progenitor cells at the epigenetic level. We also plan to develop
a new tool that will be an important addition to the zebrafish community for investigation of the
consequences of targeted epigenetic modulation of specific genes. These proposed studies will
illuminate candidate genes for targeted therapeutic approaches to identify and “unlock” pathways
in mammalian systems that are epigenetically silenced, opening new avenues for future studies
in the field of regenerative medicine.

## Key facts

- **NIH application ID:** 10132726
- **Project number:** 5F30EY031142-02
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Ashley Kramer
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $44,030
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132726

## Citation

> US National Institutes of Health, RePORTER application 10132726, Elucidating the role of DNA methyltransferases in epigenetic regulation of retinal regeneration in zebrafish (5F30EY031142-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10132726. Licensed CC0.

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