# Uncovering novel targets for retinal ganglion cell neuroprotection and axon regeneration

> **NIH NIH F32** · BOSTON CHILDREN'S HOSPITAL · 2020 · $65,310

## Abstract

Project Summary
Like other neurons of the central nervous system, retinal ganglion cells (RGCs)—the projection neurons of the
retina—fail to regenerate after injury. In glaucoma, a leading cause of blindness, degeneration of RGC axons
and their subsequent death are two key pathological events that lead to irreversible loss of vision. However, no
effective treatments to prevent RGC vulnerability and loss are available. A critical obstacle toward developing
novel therapeutics is our insufficient understanding of mechanisms that regulate RGC survival and axon
regeneration. Using mouse optic nerve crush (ONC) model, previously, we discovered that removal of
phosphatase and tensin homolog (PTEN) protein significantly promotes axon regeneration. More recently, we
leveraged ONC model and undertook a large-scale in vivo CRISPR screen to identify key regulators of such
mechanisms. Our screen revealed multiple genes whose removal from retinal cells promoted RGC survival
and/or axon regeneration. One of the strongest protective phenotypes belonged to the knockout of the c-Jun N-
terminal kinases-Interacting Protein 3 (JIP3). However, knockout of JIP3 not only fails to promote axon
regeneration in survived RGCs, it abolishes axon regeneration induced by PTEN deletion. Here, I propose
performing transcriptomic analysis of RGCs with or without JIP3 and/or PTEN at different time points after optic
nerve injury to further investigate molecular programs underlying JIP3-dependent RGC survival, and PTEN-
dependent axon regeneration. Furthermore, I will test the neuroprotective effect of JIP3 in a mouse glaucoma
model in which elevation of intraocular pressure causes RGC loss.

## Key facts

- **NIH application ID:** 10067760
- **Project number:** 1F32EY031930-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Aboozar Monavarfeshani
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10067760

## Citation

> US National Institutes of Health, RePORTER application 10067760, Uncovering novel targets for retinal ganglion cell neuroprotection and axon regeneration (1F32EY031930-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10067760. Licensed CC0.

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