# Hippo Pathway Regulation of Müller Glial Cell-mediated Retinal Regeneration

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $444,571

## Abstract

PROJECT SUMMARY/ABSTRACT
 Retinal diseases such as glaucoma, macular degeneration, and diabetic retinopathy, as well as traumatic
injury, result in loss of retinal neurons and thus sight, depriving many worldwide of one of our most valued senses.
Thus, there is a critical need to devise strategies to restore lost retinal neurons leading to vision recovery. Current
efforts in retinal regenerative medicine are heavily invested in cell replacement approaches. However, it may also
be possible to induce the mammalian retinae to undergo an intrinsic self-repair mechanism to regenerate neurons.
The retinae of non-mammalian vertebrates, such as zebrafish, are known to exhibit the remarkable ability of retinal
regeneration. Here, Müller glial cells (MGs) reprogram to proliferative, retinal progenitor-like cells that in turn
differentiate into new photoreceptors leading to restoration of vision. Unfortunately, for unknown reasons,
mammalian MGs have lost this ability, or it is dormant. Our long term goal is to identify the cellular and molecular
mechanisms blocking mammalian MG-mediated retinal regeneration. By doing so, we may be able to devise
strategies to bypass this system and thereby reawaken the regenerative potential of the mammalian retina.
 In this proposal, we will test the hypothesize that the Hippo signaling pathway actively blocks mammalian
MG-mediated retinal regeneration by preventing sustained MG proliferation and reprogramming to a retinal
progenitor-like state. Our specific aims will precisely define the requirement of Hippo signaling in negative regulation
of persistent cell cycle re-entry of MGs responding to retinal damage. We will also determine whether genetic
bypass of Hippo signaling results in MG reprogramming to a progenitor-like state. Finally, we will assess the
neurogenic potential of reprogrammed MGs.
 This project will employ a multi-disciplinary approach using genetic loss- and gain-of-function experiments,
fate mapping, epigenomics, and single cell transcriptomics. By completion of the described aims, we expect to have
identified the Hippo pathway as the endogenous molecular mechanism normally restraining MG proliferation and
reprogramming to regenerative, progenitor cells. These data will provide an essential molecular entry point from
which to further investigate novel methods to promote Müller glial cell-mediated retinal regeneration and likely have
significant influence on the field of retinal regenerative medicine. We anticipate subsequent investigation into more
translational, therapeutic methods to modulate Hippo pathway activity to promote retinal regeneration.

## Key facts

- **NIH application ID:** 10438586
- **Project number:** 5R01EY030448-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Ross Anthony Poche
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $444,571
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438586

## Citation

> US National Institutes of Health, RePORTER application 10438586, Hippo Pathway Regulation of Müller Glial Cell-mediated Retinal Regeneration (5R01EY030448-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10438586. Licensed CC0.

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