Stretch stress propels glutamine dependency and glycolysis in optic nerve head astrocytes

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dc.creatorPappenhagen, Nathaniel
dc.creatorYin, Eric
dc.creatorMorgan, Autumn B.
dc.creatorKiehlbauch, Charles C.
dc.creatorInman, Denise M.
dc.creator.orcid0000-0002-8522-4112 (Inman, Denise M.)
dc.date.accessioned2022-09-20T15:20:18Z
dc.date.available2022-09-20T15:20:18Z
dc.date.issued2022-08-05
dc.description.abstractGlaucoma is an optic neuropathy that leads to irreversible blindness, the most common subtype of which is typified by a chronic increase in intraocular pressure that promotes a stretch injury to the optic nerve head. In rodents, the predominant glial cell in this region is the optic nerve head astrocyte that provides axons with metabolic support, likely by releasing lactate produced through astrocytic glycolysis. Our primary hypothesis is that stretching of the optic nerve head astrocytes alters their metabolic activity, thereby advancing glaucoma-associated degeneration by compromising the metabolic support that the astrocytes provide to the axons in the optic nerve head. Metabolic changes in optic nerve head astrocytes were investigated by subjecting them to 24 h of 12% biaxial stretch at 1 Hz then measuring the cells' bioenergetics using a Seahorse XFe24 Analyzer. We observed significant glycolytic and respiratory activity differences between control and stretched cells, including greater extracellular acidification and lower ATP-linked respiration, yet higher maximal respiration and spare capacity in stretched optic nerve head astrocytes. We also determined that both control and stretched optic nerve head astrocytes displayed a dependency for glutamine over pyruvate or long-chain fatty acids for fuel. The increased use of glycolysis as indicated by the extracellular acidification rate, concomitant with a dependency on glutamine, suggests the need to replenish NAD + for continued glycolysis and provision of carbon for TCA cycle intermediates. Stretch alters optic nerve astrocyte bioenergetics to support an increased demand for internal and external energy.
dc.description.sponsorshipThis study was funded by the National Eye Institute, R01 EY026662 to DMI.
dc.identifier.citationPappenhagen, N., Yin, E., Morgan, A. B., Kiehlbauch, C. C., & Inman, D. M. (2022). Stretch stress propels glutamine dependency and glycolysis in optic nerve head astrocytes. Frontiers in neuroscience, 16, 957034. https://doi.org/10.3389/fnins.2022.957034
dc.identifier.issn1662-4548
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31779
dc.identifier.volume16
dc.publisherFrontiers Media S.A.
dc.relation.urihttps://doi.org/10.3389/fnins.2022.957034
dc.rights.holder© 2022 Pappenhagen, Yin, Morgan, Kiehlbauch and Inman.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceFrontiers in Neuroscience
dc.subjectastrocyte
dc.subjectglaucoma
dc.subjectglycolysis
dc.subjectmetabolism
dc.subjectoptic nerve head
dc.titleStretch stress propels glutamine dependency and glycolysis in optic nerve head astrocytes
dc.typeArticle
dc.type.materialtext

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