# Determinants of type-dependent retinal ganglion cell resilience: potential targets for neuroprotection and axon regeneration

> **NIH NIH R00** · BAYLOR COLLEGE OF MEDICINE · 2022 · $246,733

## Abstract

Project Summary/Abstract
 Neurons in the central nervous system neurons have a limited ability to survive and regenerate their
axons following injury. Damage to axons is complicit in several CNS disorders including glaucoma, a major
focus of this proposal. Interventions to protect remaining cells and induce axonal regeneration have produced
promising, yet ultimately unsatisfying, results, falling short of recovery. To improve upon these results, it is
imperative to determine why some neurons fare better than others. Retinal ganglion cells (RGCs), whose
axons pass through the optic nerve, offer a tractable system to study these processes. Our lab identified that
the progression of RGC degeneration following axonal damage by optic nerve crush (ONC) is dependent on
cell type. Additionally, multiple other labs have observed cell-type specific changes in RGC morphology and
function in glaucoma models. Moreover, axon regeneration was also cell-type restricted following two different
interventions targeting the mTor pathway after ONC. These findings demonstrate that cell-intrinsic
characteristics have a strong influence on neuron degeneration and axonal regeneration.
 In this study, I will use high throughput single-cell transcriptomic approaches to examine gene
expression in an unbiased manner in RGC populations after axonal perturbations. I will apply this approach
under three sets of conditions as strategies to identify potential targets for neuroprotection and axonal
regeneration. First, I will determine how gene expression differences emerge between resilient and susceptible
types after ONC, at stages before susceptible types are lost. This will reveal expression changes that correlate
with resilience. Second, I will assess gene expression changes induced by three established interventions that
act on different pathways and promote survival and/or axonal regeneration in distinct subsets of RGCs. This
will reveal the changes occurring in ‘rescued’ types that correlate with their improved outcomes. Third, I will
assess gene expression in two models of glaucoma with distinct disease progression to identify shared and
distinct mechanisms of degeneration. I will use insights gained from expression analyses to target candidate
genes in vivo using loss and gain-of-function methods and determine their effects on RGC survival and/or
axonal regeneration. This has important implications for understanding the different ways degeneration
progresses in neurons and has strong potential to identify novel therapeutic targets for glaucoma and other
neurodegenerative disorders.

## Key facts

- **NIH application ID:** 10445339
- **Project number:** 5R00EY029360-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Nicholas Minh Abell Tran
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $246,733
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445339

## Citation

> US National Institutes of Health, RePORTER application 10445339, Determinants of type-dependent retinal ganglion cell resilience: potential targets for neuroprotection and axon regeneration (5R00EY029360-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10445339. Licensed CC0.

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