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Shrestha Priyadarsini, Tina B McKay, John Asara, Jeremy Allegood, charles chalfant, Dimitrios Karamichos; Hyperglycemic condition altering corneal stroma environment and wound healing capacity. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6155.
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© ARVO (1962-2015); The Authors (2016-present)
Prolonged hyperglycemic condition during diabetes mellitus (DM) often leads to various ophthalmic complications, such conditions seriously affects the cornea and various other regions of the eye. This often leads to impaired vision or blindness due to decreased wound healing capacity, corneal edema, and altered epithelial basement membrane. During DM, changes in bioenergetics which affects gene expression, protein metabolism, and various signaling pathways related to proliferation and differentiation are seen. In this study, our primary goal was to compare the metabolome and lipidome of normal, Type 1 and Type 2 diabetic corneas and identify similarities and differences. Identification of the key factors that are altered in the diabetic cornea compared to a normal cornea will unveil therapeutic targets for treatment of diabetes mellitus.
Human corneas of healthy donors, Type I (T1DM), and Type 2 (T2DM) diabetic donors were obtained from NDRI and the Oklahoma Lions eye bank. Epithelium and endothelium layers were scrapped off and the corneal stroma was processed for mass spec-based metabolomics, lipidomics, western blot and TEM.
Our study analysis showed increased expression of fibrotic markers α SMA (2 folds), Col I (3.5 folds) and Col III (6 folds) expressed in both T1DM and T2DM corneas when compared to the healthy controls. Metabolomics analysis showed upregulated tryptophan metabolites regulation in DM corneas in comparison to healthy corneas which leads to the significant upregulation of Kynurenine pathway. . Increased lipids, such as sphingosine-1-phosphate, dihydrosphingosine, and dihydrosphingosine-1-phosphate were measured in diabetic corneas suggesting a link to altered lipid metabolism in DM. We also identified key metabolites like Aminoadipic acid, D.L-Pipecolic Acid and Dihydroorotate, which were significantly upregulated and could be possible novel bio-markers for identifying fibrosis caused in cornea due to DM.
We have clearly identified the multiple parameters that are altered during DM in the human cornea. Identification of key metabolites and lipids are crucial for maintaining a healthy cornea, and these findings pave the way for developing therapeutic measures in treating DM ocular complications.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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