# Correlating Genomic AMD Risk Variants with Lipid Composition and Phagocytic Function of Patient-Derived Induced Pluripotent Stem Cell (iPSC)-derived Retinal Pigment Epithelium (RPE)

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2024 · $393,500

## Abstract

PROJECT SUMMARY
Age-related macular degeneration (AMD) is one of the leading causes of blindness worldwide. Dysfunction of
the retinal pigment epithelium (RPE) is one of the primary early events during AMD. RPE cells play many
important roles in vision and helps to maintain the health and integrity of the retina and defects in this layer lead
to progressive degeneration of photoreceptor cells. Hallmarks of AMD include protein deposits called drusen
which lie underneath the retinal pigment epithelium (RPE) and can evolve into geographic atrophy or choroidal
neovascularization with consequent loss of photoreceptors. While treatments exist that slow down the course of
some forms of AMD, a permanent cure to stop the inexorable loss of vision does not exist. A critical need in the
field is a better model for early features of AMD such as drusen formation and recognition of disease-causing
mechanisms is needed. This is a difficult problem given the multifactorial nature of AMD. It is well known that
photoreceptor and retinal pigment epithelial (RPE) cells are crucially dependent on tightly controlled lipid
homeostasis to maintain function. Each day, roughly a tenth of the rod outer segments (OS) are shed and
phagocytized by the RPE, which recycle the membranes as part of the visual cycle. Given the vast amount of
cell membrane, mostly comprised of lipids and proteins that is recycled daily, it is plausible that defects in lipid
metabolism could be involved in at least some part of the disease pathology. In this project we propose to study
lipidomics in human RPE cells from patient derived iPSCs as part of the Age-Related Eye Disease Study 2
(AREDS2) which aims to identify predisposing factors, clinical features, and prognostic indicators of AMD. We
propose to differentiate iPSC lines from this study, assess potential variability between lines, and evaluate
transcriptional differences. We will then assess differences in the lipid content of ‘disease’ versus control lines
searching for potential biomarkers of disease. Lastly, we will explore functional differences between lines by
performing phagocytosis assays. Together, we hope to identify novel disease-associated biomarkers that may
ultimately lead to new therapeutic options for treating this devastating disease.

## Key facts

- **NIH application ID:** 10912469
- **Project number:** 5U01EY034594-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Dorota Skowronska-Krawczyk
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $393,500
- **Award type:** 5
- **Project period:** 2022-09-30 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10912469

## Citation

> US National Institutes of Health, RePORTER application 10912469, Correlating Genomic AMD Risk Variants with Lipid Composition and Phagocytic Function of Patient-Derived Induced Pluripotent Stem Cell (iPSC)-derived Retinal Pigment Epithelium (RPE) (5U01EY034594-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10912469. Licensed CC0.

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