# Determinants of Rod and Cone Response Characteristics

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $423,515

## Abstract

Project Summary/Abstract
Metabolic features of photoreceptors, Müller cells and retinal pigment epithelium cells
are strikingly different. Metabolic relationships between these cells are important for
retina function and survival. A key component of this metabolic ecosystem is the
extraordinary efficiency with which photoreceptors in the outer retina convert glucose to
lactate. Highly efficient glycolysis of glucose to lactate in the presence of abundant O2
and abundant mitochondria is referred to as “Aerobic glycolysis” or the “Warburg effect”.
It is a metabolic feature of retinas and also of many types of cancer cells. The molecular
mechanism responsible for the Warburg effect is unknown. We will use strategies
described in the following three specific aims to identify the molecular mechanisms that
enhance aerobic glycolysis in retinas.
In the first specific aim of this proposal we will measure metabolic flux in live cells to
reveal which steps in glycolysis are enhanced in retinas. Our preliminary findings show
that the steady state concentrations of glycolytic intermediates in retinas is very low and
that flux through those intermediates is very fast. Our preliminary findings suggest that
steps that involve production and consumption of NADH appear to be enhanced.
In the second aim we will compare retinal and RPE proteins using mass spectrometry
without and with cross-linking to determine how retinas favor reduction over oxidation of
pyruvate. These experiments will demonstrate the relative enrichment of glycolytic vs.
mitochondrial proteins in the retina and RPE. The cross-linking studies will identify
protein-protein interactions between the enzymes that catalyze reactions in the glycolytic
pathway.
In the third aim we will use in vitro assays of glycolytic enzyme activity to determine how
retinas favor reduction over oxidation of pyruvate in mitochondria. Assaying production
of lactate from glucose in the presence of enzymes that can compete for consumption of
glycolytic intermediates will test the hypothesis that glycolysis is enhanced by channeling
of glycolytic products and substrates between enzymes.

## Key facts

- **NIH application ID:** 9814976
- **Project number:** 2R01EY006641-34
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** JAMES Bryant HURLEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,515
- **Award type:** 2
- **Project period:** 1986-07-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9814976

## Citation

> US National Institutes of Health, RePORTER application 9814976, Determinants of Rod and Cone Response Characteristics (2R01EY006641-34). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9814976. Licensed CC0.

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