# Remodeling of chromatin and transcriptomic landscape to enhance optic nerve regeneration

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2021 · $439,463

## Abstract

Summary
Long distance axon regeneration is one of the most important aspects and a prerequisite for successful
functional recovery after optic nerve injuries. Although great progress has been made to enhance the
intrinsic axon regeneration ability via various approaches, long distance optic nerve regeneration reaching the
original targets in the brain remains a major challenge. We think that extending sufficient number of injured
RGC axons from different RGC subtypes into the brain should be the major tasks for functional recovery
after visual injuries. Therefore, a new strategy is needed to 1) enhance RGC survival rate, 2) identify
additional gene targets capable of enhance regeneration from a diverse subtypes of RGCs, and 3) promote
extensive long-distance optic nerve regeneration that is less affected by the inhibitory environment. During
RGC maturation, their chromatin structures change temporally, leading to changed transcriptomics
underlying the loss of intrinsic ability to support axon regeneration. Conversely, the current identified genes
that act to enhance optic nerve regeneration presumably alter the developmental changes in transcriptomics in
some way. Thus, it is important to reveal the chromatin and transcriptomics landscape of RGCs favorable
for axon regeneration, and identify key transcription factors and/or chromatin modulators underlying
such chromatin state of regenerating RGCs. In Aim 1, by performing RNA-seq, ATAC-seq and ChIP-seq of
purified RGCs at different maturation stages, and different regenerative states, we will use advanced
integrative bioinformatics analyses to reveal the chromatin and transcriptomics landscape of RGCs favorable
for axon regeneration, and identify key transcription factors and/or chromatin modulators underlying such
chromatin state of regenerating RGCs. In Aim 2, we will perform functional screening experiments to
determine their roles in regulation of RGC survival and/or optic nerve regeneration, and their underlying
mechanisms. Our recent work showed that deleting non-muscle myosin IIA/B or histone demethylase UTX,
when combined with enhanced intrinsic axon regeneration ability, could lead to extensive long-distance optic
nerve regeneration. Based on these results, in Aim 3, we will explore if combining the newly identified
transcription factors with UTX and myosin IIA/B knockout could induce long distance optic nerve regeneration
into the brain. The proposed studies will not only generate a detailed picture of changes in transcriptomics,
chromatin accessibility and epigenetic landscape of RGCs during maturation and regeneration, but also
identify novel molecular targets and optimized approaches to re-establish visual circuity.

## Key facts

- **NIH application ID:** 10224213
- **Project number:** 5R01EY031779-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Fengquan Zhou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $439,463
- **Award type:** 5
- **Project period:** 2020-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10224213

## Citation

> US National Institutes of Health, RePORTER application 10224213, Remodeling of chromatin and transcriptomic landscape to enhance optic nerve regeneration (5R01EY031779-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10224213. Licensed CC0.

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