# Human RPE metabolism and metabolite transport

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $391,500

## Abstract

   
DESCRIPTION (provided by applicant): 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:** 9829975
- **Project number:** 5R01EY026030-05
- **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:** $391,500
- **Award type:** 5
- **Project period:** 2016-01-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829975

## Citation

> US National Institutes of Health, RePORTER application 9829975, Human RPE metabolism and metabolite transport (5R01EY026030-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9829975. Licensed CC0.

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