# Understanding the role of cytosolic NADH production in maintaining aerobic glycolysis in the retina

> **NIH NIH F31** · UNIVERSITY OF WASHINGTON · 2021 · $36,130

## Abstract

ABSTRACT
Vision loss affects 1.3 billion people worldwide, with 253 million of those people experiencing
vision loss which ranges from severe to total blindness. The etiology of diseases which can
cause vision loss are highly complex, as more genes have been identified which can be
mutated to cause blindness compared to any other disease. However, many of these genes are
involved in metabolic processes. This suggests that it is imperative to have a complete
understanding of metabolism in a healthy retina so we can better understand how to treat it
when it becomes dysregulated in disease. One aspect of retinal metabolism which seems to be
very important for maintaining vision is a high level of aerobic glycolysis performed by
photoreceptors. However, we are still far from understanding how photoreceptors maintain this
high rate pyruvate to lactate conversion since they also contain functional and underused
mitochondria which could use pyruvate to more efficiently make ATP. In our preliminary
investigations into this question, we have observed that photoreceptors use GAPDH to maintain
a uniquely high cytoplasmic NADH/NAD+ ratio and that high levels of NADH could be sufficient
to drive lactate production. However, previously published results have shown that GAPDH is
not overexpressed in photoreceptors, so it is still unclear what is driving its high activity.
In aim 1 of this proposal, I will address how retinas maintain a uniquely high cytoplasmic
NADH/NAD+ ratio by performing a comparative analysis of flux through each step in glycolysis
between retinas and oxidative tissues. I predict that I will identify steps early in glycolysis which
are rate-limiting for flux through GAPDH and thus cytosolic NADH production in oxidative
tissues, but not in retinas. In aim 2 of this proposal, I will use an alternative oxidase to
specifically lower the cytoplasmic NADH/NAD+ ratio in cone photoreceptors, which will allow us
to address both the importance of cytoplasmic NADH for maintaining aerobic glycolysis, as well
as the role of photoreceptor lactate production on the health of the retinal ecosystem as a
whole.

## Key facts

- **NIH application ID:** 10132727
- **Project number:** 5F31EY031165-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Celia Bisbach
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $36,130
- **Award type:** 5
- **Project period:** 2020-03-01 → 2021-12-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10132727

## Citation

> US National Institutes of Health, RePORTER application 10132727, Understanding the role of cytosolic NADH production in maintaining aerobic glycolysis in the retina (5F31EY031165-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10132727. Licensed CC0.

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