# Spatially resolved measurements of retinal metabolism

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $316,000

## Abstract

Abstract
Understanding retinal metabolism in detail is fundamental to knowing how the retina withstands, compensates
for, or suffers from the stresses imposed by systemic changes and disease. This application takes a new
approach to understanding glycolytic and oxidative metabolism of the mammalian retina, by recording spatial
profiles of oxygen and pH in the isolated rat and mouse retina with microelectrodes, using mathematical
models of diffusion to extract information about rates of substrate utilization and waste generation, and
employing pharmacology to isolate different processes. This strategy is complimentary to previous in vivo and
in vitro approaches, but allows a separation of metabolic events in the inner and outer retina, which has rarely
been possible, and cannot be done with measurements of whole tissue metabolism. Microelectrode
approaches simultaneously allow recording of transretinal and intraretinal electroretinograms to monitor retinal
function. There are three aims. 1) Depth profiles of oxygen will be recorded in order to determine quantitatively
how the metabolism of the isolated retina compares to that in vivo, and how the inner and outer retina differ
metabolically. Photoreceptors are known to perform high rates of (anaerobic) glycolysis, but the balance
between oxidative and glycolytic energy production is not known in the inner retina, and whether this changes
depending on glucose supply. Retinal blood flow increases in response to flickering light (neurovascular
coupling), but the size of the metabolic change in the inner retina that drives this is unknown, and will be
measured here. 2) By recording depth profiles of pH in the isolated retina, the production of acidic waste will be
quantified. Glycolysis and oxidative metabolism are very different in acid production. To identify the
components of acid production, hypoxia and metabolic poisons that suppress either glycolysis or oxidative
metabolism will be used. 3) In some tissues there is evidence that glycolysis and oxidative metabolism are
compartmentalized, with a transfer of lactate and/or pyruvate from glycolytically active cells to ones that
depend more on oxidative metabolism. This concept has led to the idea that the retina uses a similar strategy,
with lactate being produced in Muller cells and shuttled to neurons. The relatively recent availability of
selective blockers of monocarboxylate transport, provides an opportunity to evaluate the importance of such
transfer quantitatively in both the inner and outer retina. All the information to be gained is fundamental to
understanding how the retina changes in disease, and what the capabilities of the inner and outer retina are for
oxidative and glycolytic metabolism under different conditions.

## Key facts

- **NIH application ID:** 9906901
- **Project number:** 5R01EY029306-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** ROBERT A. LINSENMEIER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $316,000
- **Award type:** 5
- **Project period:** 2019-05-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906901

## Citation

> US National Institutes of Health, RePORTER application 9906901, Spatially resolved measurements of retinal metabolism (5R01EY029306-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9906901. Licensed CC0.

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