# Retinal Ganglion Cell Replacement in Clinically Relevant Models of Optic Neuropathy

> **NIH NIH U24** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $1,346,020

## Abstract

The objective of this study is to generate clinically relevant models of optic neuropathy in a species that
recapitulates the anatomy and physiology of the human retina and optic nerve that can be used to optimize
allogenic transplantation of induced pluripotent stem cell (iPSC)-derived retinal ganglion cells (RGCs). We will
use the tree shrew, which has a collagenous, load-bearing lamina cribrosa and a cone-dominant retina with
fovea-level convergence onto the RGCs. We will induce and characterize two optic neuropathies in this
species, glaucoma and traumatic optic neuropathy. Simultaneously, we will optimize generation of tree shrew
optic cup organoids from fibroblasts as the source of allogenic RGCs for transplantation. We will compare the
transcriptome profile of these induced RGCs to primary tree shrew RGCs. We will optimize transplantation of
these cells in both models by identifying: 1) the optimal disease stage for transplantation, 2) the optimal
differentiation stage of the RGCs for transplantation, 3) if modulating the inner limiting membrane will improve
integration, and 4) if co-treatment a zinc chelator will improve axon outgrowth of the transplanted retinal
ganglion cells. In characterizing the two models we will quantify changes in cytokine levels, glial reactivity,
axon degeneration, and RGC death over time. Our primary outcomes for the transplantation studies will be
functional: pattern electroretinograms, in vivo calcium imaging, and ex vivo microelectrode recordings.
Secondary outcomes for will include quantification of surviving transplanted cells located within the ganglion
cell layer, the length of axons, and dendrite formation and synaptic connectivity with upstream neurons.

## Key facts

- **NIH application ID:** 10242087
- **Project number:** 5U24EY029893-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Petr Baranov
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,346,020
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242087

## Citation

> US National Institutes of Health, RePORTER application 10242087, Retinal Ganglion Cell Replacement in Clinically Relevant Models of Optic Neuropathy (5U24EY029893-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242087. Licensed CC0.

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