# Characterization of human RPE subpopulations at the single cell level

> **NIH NIH R01** · REGENERATIVE RESEARCH FOUNDATION · 2021 · $412,250

## Abstract

Project Summary / Abstract
The retinal pigment epithelium (RPE) plays a crucial role in supporting vision through a variety of activities that
maintain retinal health. A loss of RPE cells occurs early in age related macular degeneration (AMD) with a
concomitant loss of vision. AMD is the leading cause of blindness in the elderly and its incidence is expected to
increase as the US population ages, with great associated personal and economic costs. AMD can be divided
into two categories: `dry' AMD constitutes ~90% of cases and `wet' AMD the remaining ~10%. Currently no
effective treatment is available for dry AMD, but stem cell therapy holds great promise to replace the RPE cells
lost in dry AMD pathogenesis. To this end, we have identified an adult RPE stem cell (RPESC) as a potential
source for RPE cell replacement. Our previous work utilizing an animal model of AMD demonstrated the ability
of transplanted RPESC-derived RPE (RPESC-RPE) to rescue vision. We found that a progenitor stage of
RPESC-RPE maturation is more effective than fully differentiated, mature progeny at vision rescue. In this
proposal, we aim to first survey the RPE subpopulations present in the native human RPE layer, including the
RPESC, using single cell transcriptomics (Aim 1) and a cell surface screen (Aim2). In Aim 3, we assess the
cellular and molecular pathways that underlie vision benefit by transplanted RPE vision. In preliminary
experiments using an in vitro integration assay that efficiently evaluates each RPE subpopulation, we found the
RPE progenitor stage integrates more effectively than differentiated RPE progeny. We plan to confirm these in
vitro results and describe integration of individual subpopulations after transplantation in the animal model.
Furthermore, the transcripts that identify the effective RPE subpopulation describe the set of genes that are
associated with vision rescue. We use a bioinformatics approach to identify these genes and then propose
knock-down and overexpression experiments to assess their function in vitro and in vivo. Completion of these
studies will significantly increase our understanding of the RPE at cellular, molecular and functional levels.

## Key facts

- **NIH application ID:** 10186756
- **Project number:** 5R01EY029281-04
- **Recipient organization:** REGENERATIVE RESEARCH FOUNDATION
- **Principal Investigator:** Jeffrey H Stern
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,250
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10186756

## Citation

> US National Institutes of Health, RePORTER application 10186756, Characterization of human RPE subpopulations at the single cell level (5R01EY029281-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10186756. Licensed CC0.

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