# Human RPE metabolism and metabolite transport

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $136,648

## Abstract

Abstract
Energy metabolism and metabolite transport are essential for the viability and function of
the retinal pigment epithelium (RPE). Understanding these processes and their
perturbations in disease states is of fundamental importance.
Our preliminary results show reductive carboxylation is much more prominent in RPE
than in retina or other neuronal cells or tissues. We found that reductive carboxylation is
deficient in RPE cells derived from induced pluripotent stem cell (iPSC) cells made from
a Sorsby's Fundus Dystrophy (SFD) patient and under conditions of oxidative stress, a
critical component of early pathogenesis of AMD. Because of the potential disease
relevance of reductive carboxylation in RPE cells, we will examine the role of reductive
carboxylation in RPE cells using advanced tracer methodology, real time mitochondrial
function analysis and live imaging.
We observed in a well-controlled cell culture system that human RPE preferentially
exports metabolites to the retinal side. We also found that metabolite transport is
impaired in SFD iPSC-derived RPE cells. We plan to systematically investigate the
regulation of metabolite transport by extracellular structure and intracelluar state, and
identify the mechanisms of the defective transport in SFD RPE.
This proposed research will generate a reference data set of metabolites that are
preferentially exported and consumed by the RPE, determine the role of reductive
carboxylation in RPE cell metabolism, and reveal normal and disease-relevant changes
in metabolite transport in RPE. This new information can be used to develop treatment
of retinal degenerative diseases.

## Key facts

- **NIH application ID:** 9950461
- **Project number:** 3R01EY026030-05S1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jennifer Rayming Chao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $136,648
- **Award type:** 3
- **Project period:** 2020-09-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9950461

## Citation

> US National Institutes of Health, RePORTER application 9950461, Human RPE metabolism and metabolite transport (3R01EY026030-05S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9950461. Licensed CC0.

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