# Hippo Signaling in Regeneration of the Retinal Pigment Epithelium

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2021 · $30,803

## Abstract

PROJECT SUMMARY
The retinal pigment epithelium (RPE) is an essential monolayer that lies between the retina and the choroid and
supports the function and integrity of the retinal photoreceptors. The RPE maintains tissue homeostasis in the
adult mainly via long-term survival instead of cell turnover. Degeneration and atrophy of the central RPE causes
the detrimental chronic disease age-related macular degeneration (AMD), which is the leading cause of
blindness in the elderly population. A possibility for treating dry AMD in the future is by stimulating endogenous
RPE regeneration, but little is known about the mechanisms that can drive RPE regeneration in vivo. One
candidate pathway is the Hippo signaling pathway, as it plays a role in regulating cell proliferation and
regeneration in many tissues and is also required in the developing RPE for cell fate specification. In
developmental studies, we and others have discovered that Neurofibromin 2 (NF2) is critical for balancing RPE
growth and proliferation. My preliminary data suggests that modulation of Hippo signaling through Nf2 disruption
in the adult stimulates proliferation and differentiation of the RPE following injury. This proposal aims to determine
how genetic manipulation of Hippo signaling promotes an intrinsic proliferative and regenerative response in the
mammalian RPE. In Aim 1, I will characterize the role of NF2 in promoting RPE regeneration after injury in the
adult. I have established an injury paradigm, in which I chemically injure the RPE of mice. Regeneration will be
assessed on a cellular level by expression, co-localization, and quantification of RPE and proliferative markers,
and on a functional level by electroretinography. In Aim 2, I will determine the mechanism by which YAP regulates
RPE specification and maintenance in the RPE. Several studies demonstrate that YAP is required for RPE
identity in the embryo and adult; however, the molecular mechanism is not well understood. Here, I will
investigate the hypothesis that YAP and the transcription factor TEAD directly regulate expression of RPE-
specific genes by using chromatin immunoprecipitation and luciferase assays. The results of these experiments
will reveal how YAP regulates RPE specification, and how the Hippo signaling pathway can be modulated to
promote RPE regeneration. Understanding the cellular and molecular mechanisms that promote RPE
regeneration will help identify and develop therapeutic strategies for AMD.

## Key facts

- **NIH application ID:** 10232659
- **Project number:** 1F31EY032772-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Sara Ramirez
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $30,803
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232659

## Citation

> US National Institutes of Health, RePORTER application 10232659, Hippo Signaling in Regeneration of the Retinal Pigment Epithelium (1F31EY032772-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10232659. Licensed CC0.

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