# Deconstructing and Modeling the Single Cell Architecture of the Age-Related Macular Degeneration Retina and RPE/Choroid

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2021 · $580,003

## Abstract

Vision requires an orchestrated coordination between all parts of the eye. Of all
the parts, the retina is the most vital for normal perception of an image. It is a
precisely layered structure lining the surface of the back of the eye, comprising
many millions of cells packed together in a tightly knit network. The optic nerve
connects the retina with the brain. The retina not only receives light, but also
processes it, and transmits downstream signals to the midbrain and the thalamus.
When the retina becomes diseased as in age-related macular degeneration
(AMD), the unfortunate result can be blindness which is the most feared disability.
Progress in the genetics of AMD has been substantial, yet the translation of these
results has been slow to reach the clinic. Reasons for this delay include lack of
suitable animal models to perform functional genetics because of anatomical
differences with humans, insufficient understanding about the specific cell types
involved in the initiation of AMD and an incomplete understanding of human retinal
biology. It is challenging to assess if the early pathology in AMD affects diverse cell
populations versus highly specific cell types. Recent technologic breakthroughs in
single-cell RNA-seq (scRNA-seq) have made it possible to measure gene
expression in single cells, paving the way for exploring cellular heterogeneity.
Collaborating with the Alabama Eye Bank, we will deeply sample human retinal
cells and RPE/choroid, fully characterize cell diversity, and elucidate the functional
roles of findings from genome- wide association studies for AMD. We propose the
following aims. Aim 1 will generate single and bulk RNA-seq data from eyes of 20
healthy adults, 24 early/intermediate AMD and 6 GA donors. Aim 2 will
characterize cell diversity and cell gene expression in normal human retina and
RPE/choroid, and compare these results to AMD eyes. Aim 3 will infer cell-type
specific eQTLs and integrate these results with AMD GWAS to identify target
genes. These pioneering studies leverage novel methods and interdisciplinary
expertise to characterize cell type-specific gene expression in human retina and
supporting tissues. By detailed characterization of the cell atlases in four
geographical areas in human eye, our study will provide novel insights into cell-
type specific functions that can power precision therapeutic targeting of AMD.

## Key facts

- **NIH application ID:** 10242936
- **Project number:** 5R01EY031209-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Christine A Curcio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $580,003
- **Award type:** 5
- **Project period:** 2020-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242936

## Citation

> US National Institutes of Health, RePORTER application 10242936, Deconstructing and Modeling the Single Cell Architecture of the Age-Related Macular Degeneration Retina and RPE/Choroid (5R01EY031209-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242936. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*