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

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $401,918

## Abstract

PROJECT SUMMARY
The retina, an outgrowth of the brain, is often referred to as the “window of the brain”. The retina and the brain
are both associated with various neurological diseases, including Alzheimer's disease (AD) and age-related
macular degeneration (AMD). AD and AMD share similar neuropathological conditions, with AD characterized
by extra-cellular amyloid plaques and neurofibrillary tangles, and AMD diagnosed by the presence of drusen
deposits. Mounting evidence suggests that AD also results in visual deficits and pathological changes in the
retinas of AD patients, including the extensive loss of optic nerve and retinal ganglion cells, thinning of the retinal
nerve fiber layer, and vascular abnormalities. Although the biochemical analysis of drusen deposits in AMD has
shown remarkable similarities to the AD deposits, the underlying molecular mechanisms that lead to their
similarity are still unknown.
This study aims to identify shared cell types and common cellular pathways between AD and AMD through
comparative single-cell data analysis. To achieve this goal, we propose two aims. Aim 1 will harmonize BRAIN
Initiative generated single-cell RNA-seq (scRNA-seq) and single-nucleus RNA-seq (snRNA-seq) data with
snRNA-seq data generated from AD brains to produce a fully harmonized, denoised, batch effect corrected, and
annotated sc/snRNA-seq dataset that will be ready for differential gene expression and cell-cell communication
analysis. Using the harmonized data obtained from Aim 1, Aim 2 will conduct cell-type-specific differential gene
expression and cell-cell communication analysis between AD and normal brains. We will further conduct
comparative analysis with cell-type-specific changes obtained from our parent R01 that focuses on AMD. By
comparing the changes in AD brains and AMD eyes at the cell-type-specific level, we will identify shared cell
types and common pathways between these two diseases. Findings from this application will address key
knowledge gaps in the degeneration mechanisms of AD and AMD, elucidate the connections between these two
diseases, and seed cell-specific functional studies, in vivo modeling, and precision therapeutic targeting of both
AD and AMD.

## Key facts

- **NIH application ID:** 10835305
- **Project number:** 3R01EY031209-04S1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MARGARET M DEANGELIS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $401,918
- **Award type:** 3
- **Project period:** 2020-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10835305

## Citation

> US National Institutes of Health, RePORTER application 10835305, Deconstructing and Modeling the Single Cell Architecture of the Age-Related Macular Degeneration Retina and RPE/Choroid (3R01EY031209-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10835305. Licensed CC0.

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