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

Abstract Corneal 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 un...

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Autores principales: Amy E. Whelchel, Sarah E. Nicholas, Jian-Xing Ma, Dimitrios Karamichos
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:e371bc0601aa45068d729c0d4278fd222021-12-02T16:10:37ZNerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study10.1038/s41598-021-93164-12045-2322https://doaj.org/article/e371bc0601aa45068d729c0d4278fd222021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93164-1https://doaj.org/toc/2045-2322Abstract Corneal 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.Amy E. WhelchelSarah E. NicholasJian-Xing MaDimitrios KaramichosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Amy E. Whelchel
Sarah E. Nicholas
Jian-Xing Ma
Dimitrios Karamichos
Nerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study
description Abstract Corneal 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.
format article
author Amy E. Whelchel
Sarah E. Nicholas
Jian-Xing Ma
Dimitrios Karamichos
author_facet Amy E. Whelchel
Sarah E. Nicholas
Jian-Xing Ma
Dimitrios Karamichos
author_sort Amy E. Whelchel
title Nerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study
title_short Nerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study
title_full Nerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study
title_fullStr Nerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study
title_full_unstemmed Nerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study
title_sort nerve influence on the metabolism of type i and type ii diabetic corneal stroma: an in vitro study
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/e371bc0601aa45068d729c0d4278fd22
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