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.

Details

Title
Nerve influence on the metabolism of type I and type II diabetic corneal stroma: an in vitro study
Author
Whelchel, Amy E 1 ; Nicholas, Sarah E 2 ; Jian-Xing, Ma 3 ; Karamichos Dimitrios 4 

 University of Oklahoma Health Sciences Center, Department of Physiology, Oklahoma City, USA (GRID:grid.266902.9) (ISNI:0000 0001 2179 3618) 
 University of North Texas Health Science Center, North Texas Eye Research Institute, Fort Worth, USA (GRID:grid.266871.c) (ISNI:0000 0000 9765 6057); University of North Texas Health Science Center, Department of Pharmaceutical Sciences, Fort Worth, USA (GRID:grid.266871.c) (ISNI:0000 0000 9765 6057) 
 University of Oklahoma Health Sciences Center, Department of Physiology, Oklahoma City, USA (GRID:grid.266902.9) (ISNI:0000 0001 2179 3618); Harold Hamm Oklahoma Diabetes Center, Oklahoma City, USA (GRID:grid.266902.9) 
 University of North Texas Health Science Center, North Texas Eye Research Institute, Fort Worth, USA (GRID:grid.266871.c) (ISNI:0000 0000 9765 6057); University of North Texas Health Science Center, Department of Pharmaceutical Sciences, Fort Worth, USA (GRID:grid.266871.c) (ISNI:0000 0000 9765 6057); University of North Texas Health Science Center, Department of Pharmacology and Neuroscience, Fort Worth, USA (GRID:grid.266871.c) (ISNI:0000 0000 9765 6057) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2547167198
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.