# Determinants of Rod and Cone Response Characteristics

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2024 · $441,250

## Abstract

Project Summary/Abstract
Metabolic relationships between retina and RPE are essential for retina function and survival.
Biochemical comparisons of explanted retina to RPE/choroid have revealed striking metabolic
differences. Retinas consume glucose rapidly and convert most of it to lactate. Cultured RPE
cells and RPE/choroid consume glucose more slowly than retinas. RPE/choroid tissue can
oxidize many types of fuels as an alternative to glucose. We proposed that retina and
RPE/choroid function synergistically as a “metabolic ecosystem”. RPE/choroid minimizes its
own consumption of glucose so more glucose can be delivered to the retina.
The simple model we proposed was based on measurements of energy metabolism in cultured
cells or in retinal or RPE/choroid explants. Those types of experiments do not prove that these
types of metabolic interactions occur in the eye of a living animal. The experiments in this
proposal test this idea more directly and more rigorously. We will measure metabolic flux in
tissue explants and we will measure it in living mice in which 13C labeled fuels are delivered via
a jugular vein catheter. We will use retinas and RPE/choroid from mice in which genes encoding
specific enzymes required for metabolism have been disrupted. Our 1st aim is to Identify
biochemical changes in degenerated retinas that cause glycolytic intermediates upstream of
pyruvate kinase to accumulate. For our 2nd aim we collaborate with other labs that have
generated mice with mutations that disrupt specific metabolic activities in retinas. Our 3rd aim is
to analyze changes in metabolic interactions caused by disrupted RPE metabolism. Aim 4 will
complete metabolic analyses of mouse models with metabolic changes designed to slow
degeneration of photoreceptors by enhancing glycolysis in rods and by suppressing it in RPE.
Our findings will help the vision community recognize therapeutic strategies that may
succesfully treat multiple types of retinal degenerations.

## Key facts

- **NIH application ID:** 10977530
- **Project number:** 2R01EY006641-38A1
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** JAMES Bryant HURLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $441,250
- **Award type:** 2
- **Project period:** 1986-07-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10977530

## Citation

> US National Institutes of Health, RePORTER application 10977530, Determinants of Rod and Cone Response Characteristics (2R01EY006641-38A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10977530. Licensed CC0.

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