# Mitochondrial pyruvate transport in retinal health and disease

> **NIH NIH R01** · WEST VIRGINIA UNIVERSITY · 2024 · $373,198

## Abstract

PROJECT SUMMARY/ABSTRACT
The retina is the most metabolically active neuronal tissue in the human body. The defect in the
energy metabolism of photoreceptor neurons and their supporting cells including glia and retinal
pigment epithelium (RPE), emerges as an important underlying cause for retinal degenerative
diseases such as inherited retinal degeneration and aging-related macular degeneration (AMD).
Previous studies and data from our lab support that photoreceptors, glial cells, and RPE are
biochemically adapted to form a metabolic ecosystem: 1) RPE transports glucose from choroid
blood supply to photoreceptors; 2) Photoreceptors metabolize most of the glucose into lactate; 3)
Lactate inhibits glycolysis in RPE to facilitate glucose transport; 4) Lactate stimulate Müller glia to
synthesize glutamine for photoreceptors. The long term goal of this project is to define the
metabolic interactions between photoreceptors and Müller glia and between RPE and outer retina
in vivo and identify their roles in retinal function and degeneration.
Mitochondrial pyruvate carrier (MPC) controls the entry of pyruvate from glycolysis into
mitochondria for oxidative metabolism. We recently found that the deletion of MPC in the retina
depletes glutamine and glutamate, inhibits glutamine utilization and enhancing ketone body
oxidation, resulting in a progressive decline of visual function and retinal degeneration. Our
preliminary data showed that the deletion of MPC in photoreceptors causes much milder
phenotype than whole retina knockout, supporting the metabolic interaction that lactate is utilized
by other cells. The objective of this proposal is to investigate the roles of mitochondrial pyruvate
transport in photoreceptor, Müller cells and RPE in metabolic interactions, visual function, and
retinal survival. We plan to conditionally knockout MPC in photoreceptors, glia or RPE separately
and rigorously test our hypothesis using advanced tracer methodology, mass spectrometry, in
vivo infusion with 13C tracers, high-resolution imaging of metabolites, visual function tests, optical
coherence tomography, and transmission electron microscopy.
The outcome of this research will establish a conceptual framework for retinal metabolism that
describes how glucose is transported and utilized in different retinal cells and describes how
disruption of metabolism in one kind of retinal cells impacts the metabolism, function, and viability
of other retinal cells. This new knowledge will provide the basis for understanding the
mechanisms of retinal degenerative diseases and lay the foundation for developing new
treatments.

## Key facts

- **NIH application ID:** 10747348
- **Project number:** 5R01EY031324-04
- **Recipient organization:** WEST VIRGINIA UNIVERSITY
- **Principal Investigator:** Jianhai Du
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $373,198
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10747348

## Citation

> US National Institutes of Health, RePORTER application 10747348, Mitochondrial pyruvate transport in retinal health and disease (5R01EY031324-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10747348. Licensed CC0.

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