# Stimulation of Retinal Regeneration

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $377,087

## Abstract

Abstract
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Like other areas of the nervous system, the retina is subject to many acquired and inherited neuronal
degenerative diseases. Since the retina provides the input for all visual sensory information to the brain, the
loss of cells results in visual impairment and potentially complete blindness. Many retinal degenerative
diseases affect only a subset of the retinal cells, although, frequently in more advanced disease, loss and
reorganization of the entire retina can occur. In mammals, there is very limited regeneration of the
degenerated cells; however, in fish, new neurons of all types regenerate from Müller glia (MG) following
retinal damage and they are functionally integrated into the existing circuitry. Although mammals, including
people, lack this ability, MG, the cellular source for regeneration, are present in all vertebrate retinas. We
hypothesize that regeneration from mammalian MG is limited because they fail to express the proneural
program of gene expression after injury. We have found that viral over-expression of a proneural
transcription factor can partly reprogram mammalian MG to a neurogenic state in vitro. For in vivo
confirmation, we generated a transgenic mouse to express Ascl1 in MG. When we induce Ascl1
expression in adult MG, the combination of Ascl1 and histone deacetylase (HDAC) inhibition can stimulate
new neuron production from MG in adult mice after NMDA induced damage. The MG-derived neurons
primarily resemble bipolar or amacrine cells, and form connections with the existing retinal circuitry. These
results show for the first time that functional neurons can be regenerated in an adult mammalian retina and
properly integrate within the existing host circuit, but raise a key question: Why do the MG only produce
bipolar cells and amacrine cells? In this proposal we outline studies to better understand, and potentially
overcome, the barriers to regeneration in mammalian retina.
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## Key facts

- **NIH application ID:** 10144447
- **Project number:** 5R01EY021482-11
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** THOMAS A REH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,087
- **Award type:** 5
- **Project period:** 2011-04-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144447

## Citation

> US National Institutes of Health, RePORTER application 10144447, Stimulation of Retinal Regeneration (5R01EY021482-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10144447. Licensed CC0.

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