Establishment of a 3D In Vitro Model to Accelerate the Development of Human Therapies against Corneal Diabetes.

To establish an in vitro model that would mirror the in vivo corneal stromal environment in diabetes (DM) patients.Human corneal fibroblasts from Healthy (HCFs), Type 1DM (T1DM) and Type 2DM (T2DM) donors were isolated and cultured for 4 weeks with Vitamin C stimulation in order to allow for extrace...

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Main Authors: Shrestha Priyadarsini, Akhee Sarker-Nag, Tyler G Rowsey, Jian-Xing Ma, Dimitrios Karamichos
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5179241?pdf=render
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author Shrestha Priyadarsini
Akhee Sarker-Nag
Tyler G Rowsey
Jian-Xing Ma
Dimitrios Karamichos
author_facet Shrestha Priyadarsini
Akhee Sarker-Nag
Tyler G Rowsey
Jian-Xing Ma
Dimitrios Karamichos
author_sort Shrestha Priyadarsini
collection DOAJ
description To establish an in vitro model that would mirror the in vivo corneal stromal environment in diabetes (DM) patients.Human corneal fibroblasts from Healthy (HCFs), Type 1DM (T1DM) and Type 2DM (T2DM) donors were isolated and cultured for 4 weeks with Vitamin C stimulation in order to allow for extracellular matrix (ECM) secretion and assembly.Our data indicated altered cellular morphology, increased cellular migration, increased ECM assembly, and severe mitochondrial damage in both T1DM and T2DMs when compared to HCFs. Furthermore, we found significant downregulation of Collagen I and Collagen V expression in both T1DM and T2DMs. Furthermore, a significant up regulation of fibrotic markers was seen, including α-smooth muscle actin in T2DM and Collagen III in both T1DM and T2DMs. Metabolic analysis suggested impaired Glycolysis and Tricarboxylic acid cycle (TCA) pathway.DM has significant effects on physiological and clinical aspects of the human cornea. The benefits in developing and fully characterizing our 3D in vitro model are enormous and might provide clues for the development of novel therapeutics.
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spelling doaj.art-6b057d7905754a3ca6c7af0e87b4986a2022-12-22T01:54:23ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-011112e016884510.1371/journal.pone.0168845Establishment of a 3D In Vitro Model to Accelerate the Development of Human Therapies against Corneal Diabetes.Shrestha PriyadarsiniAkhee Sarker-NagTyler G RowseyJian-Xing MaDimitrios KaramichosTo establish an in vitro model that would mirror the in vivo corneal stromal environment in diabetes (DM) patients.Human corneal fibroblasts from Healthy (HCFs), Type 1DM (T1DM) and Type 2DM (T2DM) donors were isolated and cultured for 4 weeks with Vitamin C stimulation in order to allow for extracellular matrix (ECM) secretion and assembly.Our data indicated altered cellular morphology, increased cellular migration, increased ECM assembly, and severe mitochondrial damage in both T1DM and T2DMs when compared to HCFs. Furthermore, we found significant downregulation of Collagen I and Collagen V expression in both T1DM and T2DMs. Furthermore, a significant up regulation of fibrotic markers was seen, including α-smooth muscle actin in T2DM and Collagen III in both T1DM and T2DMs. Metabolic analysis suggested impaired Glycolysis and Tricarboxylic acid cycle (TCA) pathway.DM has significant effects on physiological and clinical aspects of the human cornea. The benefits in developing and fully characterizing our 3D in vitro model are enormous and might provide clues for the development of novel therapeutics.http://europepmc.org/articles/PMC5179241?pdf=render
spellingShingle Shrestha Priyadarsini
Akhee Sarker-Nag
Tyler G Rowsey
Jian-Xing Ma
Dimitrios Karamichos
Establishment of a 3D In Vitro Model to Accelerate the Development of Human Therapies against Corneal Diabetes.
PLoS ONE
title Establishment of a 3D In Vitro Model to Accelerate the Development of Human Therapies against Corneal Diabetes.
title_full Establishment of a 3D In Vitro Model to Accelerate the Development of Human Therapies against Corneal Diabetes.
title_fullStr Establishment of a 3D In Vitro Model to Accelerate the Development of Human Therapies against Corneal Diabetes.
title_full_unstemmed Establishment of a 3D In Vitro Model to Accelerate the Development of Human Therapies against Corneal Diabetes.
title_short Establishment of a 3D In Vitro Model to Accelerate the Development of Human Therapies against Corneal Diabetes.
title_sort establishment of a 3d in vitro model to accelerate the development of human therapies against corneal diabetes
url http://europepmc.org/articles/PMC5179241?pdf=render
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