# Respiration in vivo in the Retina and RPE

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2021 · $264,750

## Abstract

Project Summary/Abstract
Metabolic fuels from the choroidal blood must pass through the retinal pigment epithelium (RPE)
to reach photoreceptors in the retina. The retina and RPE have unique specialized metabolic
features that facilitate this flow of nutrients. In previous studies we showed that the RPE
minimizes glycolysis so that more glucose can reach the retina. More recently we showed that
the retina, which is hypoxic in the eye of a living animal, transfers electrons from mitochondrial
respiration to fumarate to make succinate instead of transferring the electrons to oxygen to
make water. We also showed that succinate made and released by the retina can fuel oxygen
consumption by the RPE. We have proposed a model for energy metabolism in the vertebrate
eye in which succinate transfers reducing power from the hypoxic retina to the oxygen rich RPE.
After succinate is oxidized by RPE cells, its carbons can be recycled from the RPE back to the
retina to accept more electrons and transfer them to oxygen in the RPE.
We reported recently several lines of evidence that support this model for a succinate-mediated
metabolic cycle in the eye. The evidence so far is based on ex vivo analyses of healthy,
functioning retina and RPE/choroid living tissues. However, it also is important to establish to
what extent this metabolic cycle occurs in vivo, i.e. in the eyes of living animals.
Recently we established an experimental protocol in which we infuse 13C labeled metabolic
fuels including succinate and malate through catheters into the jugular veins of mice. We then
measure the time course and steady state levels of incorporation of 13C into metabolites in the
retina and RPE/choroid. In Aim 1 of this proposal we will confirm our initial findings that the
succinate cycle occurs in vivo and we will optimize the infusion protocols. In Aim 2 we will use
in vivo infusion to show how circadian and diurnal cycles influence metabolic flux between the
retina and RPE. In Aim 3 we will explore strategies to exploit the succinate cycle to slow
degeneration of photoreceptors in mouse models of retinal degeneration.

## Key facts

- **NIH application ID:** 10190455
- **Project number:** 1R21EY032597-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** JAMES Bryant HURLEY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $264,750
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190455

## Citation

> US National Institutes of Health, RePORTER application 10190455, Respiration in vivo in the Retina and RPE (1R21EY032597-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10190455. Licensed CC0.

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