# Characterization of the nascent retinal proteome regulating Hippo signaling during damage

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2024 · $240,000

## Abstract

PROJECT SUMMARY/ABSTRACT
 Retinal degenerative diseases such as age-related macular degeneration and glaucoma, as well as traumatic
injury, typically lead to loss of retinal neurons and thus sight. Therefore, there is a critical need to develop therapies
to regenerate lost retinal neurons for vision restoration. The ability for this type of intrinsic self-repair naturally occurs
in the zebrafish retina. Here, in response to retinal damage, the Müller glial cells (MGs) reprogram to a proliferative,
progenitor state capable of giving rise to new retinal neurons that integrate into the pre-existing retinal circuitry and
restore vision. While mammalian MGs do not exhibit the regenerative potential of the zebrafish, they have similar
gene expression and homeostatic roles. Additionally, in response to damage, mouse MGs display very limited and
transient entry into the cell cycle. These data suggest that an intrinsic proliferative and/or regenerative block likely
prevents mammalian MGs from undergoing sustained cell cycle re-entry and acquiring a multipotential progenitor-
like state. Recently, it was shown that the Hippo signaling pathway functions to repress sustained activity of the
TEAD transcription cofactor YAP, which is required for MG proliferation and reprogramming. By manipulating the
Hippo pathway, mammalian MGs might be able to elicit a robust regenerative response analogous to the zebrafish.
However, the upstream components that trigger initial YAP activation in MGs and subsequent repression by Hippo
are still completely unknown thereby limiting molecular entry points for therapeutic intervention. To complicate
matters, the Hippo pathway responds to a wide variety of context-dependent biochemical and biophysical inputs.
To move the field forward with an eye toward clinical translation, we must identify the MG-specific
regulators of YAP and the Hippo pathway. Therefore, this proposal aims to use cell type-specific metabolic
labeling and purification of proteins followed by mass spectroscopy on damaged mouse retinae. This approach,
which has yet to be performed on the mammalian retina, will allow us to decipher the nascent proteomes of
damaged photoreceptors and ganglion cells along with the immediate MG response during the period of YAP
activation and subsequent Hippo signaling. This information will generate new hypotheses and lay the
foundation for future studies aimed at broadening potential therapeutic targets for modulation of the Hippo
pathway to promote retinal regeneration.

## Key facts

- **NIH application ID:** 10979311
- **Project number:** 1R21EY035812-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Ross Anthony Poche
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $240,000
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979311

## Citation

> US National Institutes of Health, RePORTER application 10979311, Characterization of the nascent retinal proteome regulating Hippo signaling during damage (1R21EY035812-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10979311. Licensed CC0.

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