# Characterizing Human RPE Cell Proliferation to Advance Endogenous Regeneration

> **NIH NIH R01** · REGENERATIVE RESEARCH FOUNDATION · 2022 · $546,313

## Abstract

Project Summary / Abstract
Decades of study have demonstrated that adult human retinal pigment epithelium (RPE) cells have strong
proliferative capacity in vitro, which indicates that the RPE layer has the possibility of self-repair. We have shown
that adult RPE from elderly donors or donors with age-related macular degeneration (AMD) can proliferate in
culture and produce a near-native, renewed RPE monolayer. Despite this, RPE cells in vivo do not regenerate
the damaged cobblestone RPE layer in patients with degenerating cells, such as those with dry AMD. The
environment in vivo must effectively prevent repair of the cobblestone RPE monolayer, either through lack of
mitogens or inhibitory molecules or a combination of both. The overarching goal of these studies is to achieve
safe, controlled proliferation of endogenous RPE cells to enable self-repair of the RPE layer in patients with
AMD. The objective of this proposal is to characterize the environmental factors that positively and negatively
control the proliferation of adult human RPE cells. The first specific aim is to characterize the adult human RPE
cell surfaceome on dividing and non-dividing cells using an innovative mass spectrometry and bioinformatic
platform. This will provide the first comprehensive analysis of the molecules on the RPE plasma membrane and
reveal cell surface receptors and secreted proteins that respond to environmental factors impacting cell division.
Investigating both normal and AMD RPE will provide a greater understanding of how RPE cells change with
disease. The second specific aim is to examine a transcriptional network we have identified that is associated
with adult human RPE cell proliferation to determine which molecules are critical. To do this efficiently, we will
first employ CRISPRi, then additional functional screens. The third specific aim will examine whether exogenous
factors can activate proliferation of quiescent, cobblestone human RPE, including those in situ on Bruch’s
membrane explants, and those from patients with AMD. In addition to the main objective, this study will generate
new knowledge about RPE molecules that can be used to target RPE in vivo. The proposed work also has the
potential to improve RPE cell proliferation ex vivo for more efficient cell manufacturing. Most importantly, this
study will create a foundation for safely stimulating RPE cell proliferation in vivo. Endogenous activation of RPE
cell proliferation to counteract RPE cell loss in AMD has the potential to avoid surgery and immunosuppression
involved in RPE cell transplantation, which would greatly benefit the elderly AMD patient population.

## Key facts

- **NIH application ID:** 10337229
- **Project number:** 5R01EY032138-02
- **Recipient organization:** REGENERATIVE RESEARCH FOUNDATION
- **Principal Investigator:** SALLY TEMPLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $546,313
- **Award type:** 5
- **Project period:** 2021-02-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337229

## Citation

> US National Institutes of Health, RePORTER application 10337229, Characterizing Human RPE Cell Proliferation to Advance Endogenous Regeneration (5R01EY032138-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10337229. Licensed CC0.

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