Nerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study

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dc.creatorWhelchel, Amy E.
dc.creatorNicholas, Sarah E.
dc.creatorMa, Jian-Xing
dc.creatorKaramichos, Dimitrios
dc.creator.orcid0000-0002-8761-3824 (Karamichos, Dimitrios)
dc.date.accessioned2022-09-20T20:19:47Z
dc.date.available2022-09-20T20:19:47Z
dc.date.issued2021-07-01
dc.description.abstractCorneal innervation plays a major role in the pathobiology of diabetic corneal disease. However, innervation impact has mainly been investigated in the context of diabetic epitheliopathy and wound healing. Further studies are warranted in the corneal stroma-nerve interactions. This study unravels the nerve influence on corneal stroma metabolism. Corneal stromal cells were isolated from healthy (HCFs) and diabetes mellitus (Type1DM and Type2 DM) donors. Cells were cultured on polycarbonate membranes, stimulated by stable Vitamin C, and stroma-only and stroma-nerve co-cultures were investigated for metabolic alterations. Innervated compared to stroma-only constructs exhibited significant alterations in pyrimidine, glycerol phosphate shuttle, electron transport chain and glycolysis. The most highly altered metabolites between healthy and T1DMs innervated were phosphatidylethanolamine biosynthesis, and pyrimidine, methionine, aspartate metabolism. Healthy and T2DMs main pathways included aspartate, glycerol phosphate shuttle, electron transport chain, and gluconeogenesis. The metabolic impact on T1DMs and T2DMs was pyrimidine, purine, aspartate, and methionine. Interestingly, the glucose-6-phosphate and oxaloacetate was higher in T2DMs compared to T1DMs. Our in vitro co-culture model allows the examination of key metabolic pathways corresponding to corneal innervation in the diabetic stroma. These novel findings can pave the way for future studies to fully understand the metabolic distinctions in the diabetic cornea.
dc.description.sponsorshipThe study was supported by National Eye Institute Grant [EY028949].
dc.identifier.citationWhelchel, A. E., Nicholas, S. E., Ma, J. X., & Karamichos, D. (2021). Nerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study. Scientific reports, 11(1), 13627. https://doi.org/10.1038/s41598-021-93164-1
dc.identifier.issn2045-2322
dc.identifier.issue1
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31791
dc.identifier.volume11
dc.publisherSpringer Nature
dc.relation.urihttps://doi.org/10.1038/s41598-021-93164-1
dc.rights.holder© The Author(s) 2021
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientific Reports
dc.subject.meshCell Line
dc.subject.meshCells, Cultured
dc.subject.meshCorneal Diseases / etiology
dc.subject.meshCorneal Diseases / metabolism
dc.subject.meshCorneal Diseases / pathology
dc.subject.meshCorneal Stroma / innervation
dc.subject.meshCorneal Stroma / metabolism
dc.subject.meshCorneal Stroma / pathology
dc.subject.meshDiabetes Mellitus, Type 1 / complications
dc.subject.meshDiabetes Mellitus, Type 1 / metabolism
dc.subject.meshDiabetes Mellitus, Type 1 / pathology
dc.subject.meshDiabetes Mellitus, Type 2 / complications
dc.subject.meshDiabetes Mellitus, Type 2 / metabolism
dc.subject.meshDiabetes Mellitus, Type 2 / pathology
dc.subject.meshEnergy Metabolism
dc.subject.meshGlucose / metabolism
dc.subject.meshHumans
dc.subject.meshMetabolic Networks and Pathways
dc.subject.meshMetabolome
dc.subject.meshNerve Tissue / metabolism
dc.subject.meshNerve Tissue / pathology
dc.titleNerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study
dc.typeArticle
dc.type.materialtext

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