# Glutamine as an alternative fuel source for photoreceptors

> **NIH NIH K08** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $232,607

## Abstract

SUMMARY: Photoreceptor cell death is the ultimate cause of vision loss in many retinal disorders, and there is
an unmet need for neuroprotective therapies to improve their survival. The bioenergetic requirements of
photoreceptors rival that of neoplastic tissue. To meet this demand, photoreceptors have unique metabolic
adaptations to budget their bioenergetic needs. One such adaptation is the utilization of aerobic glycolysis, so
glucose metabolism has been central in the study of photoreceptor physiology. Even so, fuels other than
glucose may be used to meet the needs of photoreceptors, especially during times of bioenergetic stress.
Given their crowded, nutrient-limited environment, photoreceptors may have evolved to remove any rigid
constraints on fuel sources. This proposal will provide fundamental insight into the contribution of a potential
alternative fuel source to photoreceptor metabolism, function, and survival, while providing the substrate for
critical skills in career development. The long-term goal of this work is to develop the skills needed to pursue
novel therapies that prevent vision loss in photoreceptor degenerations as an independent clinician-scientist.
 The scientific objective of this K08 proposal is to test the hypothesis that glutamine is a key fuel
source to maintain photoreceptor biomass, regulate redox balance, and boost photoreceptor survival during
periods of nutrient deprivation. We propose to assess the metabolic fate of glutamine in vitro and in vivo using
stable-isotope metabolic flux analysis and its contribution to photoreceptor redox balance, function, and
survival by disrupting glutamine catabolism in a photoreceptor-specific, glutaminase (Gls) conditional knockout
mouse. Two focused specific aims will be utilized to investigate our hypothesis: 1) Determine how glutamine
contributes to components of photoreceptor biomass and regulates redox homeostasis.; 2) Determine how
photoreceptors utilize glutamine as an alternative fuel source to promote survival during outer retinal stress.
 The career development objective is to cultivate the skills and mentorship required to develop
expertise in the application, acquisition, and analysis of metabolomics data, and to achieve scientific
independence. The coursework, seminars, and mentorship will complement the research. The multi-
disciplinary team of mentors, each with a complementary skill set, is deeply committed to the principal
investigator’s success. The Department of Ophthalmology and Visual Sciences and the University of Michigan
has world-class faculty and facilities, and the research proposed fits exceptionally well with the internationally
recognized expertise in metabolism and metabolomics at the University of Michigan and within the mentoring
team. The institutional environment, mentoring, and career development plan maximize the success of the
research aims and the ability of the principal investigator to become an independent clinician-scientist studyin...

## Key facts

- **NIH application ID:** 10471802
- **Project number:** 5K08EY031757-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Thomas Joseph Wubben
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $232,607
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471802

## Citation

> US National Institutes of Health, RePORTER application 10471802, Glutamine as an alternative fuel source for photoreceptors (5K08EY031757-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10471802. Licensed CC0.

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