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建立3D体外模型以加速抗角膜糖尿病人类疗法的开发。

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

作者信息

Priyadarsini Shrestha, Sarker-Nag Akhee, Rowsey Tyler G, Ma Jian-Xing, Karamichos Dimitrios

机构信息

Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.

Department of Biology and Chemistry, East Central University, Ada, Oklahoma, United States of America.

出版信息

PLoS One. 2016 Dec 22;11(12):e0168845. doi: 10.1371/journal.pone.0168845. eCollection 2016.

DOI:10.1371/journal.pone.0168845
PMID:28005998
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5179241/
Abstract

PURPOSE

To establish an in vitro model that would mirror the in vivo corneal stromal environment in diabetes (DM) patients.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

摘要

目的

建立一种能模拟糖尿病（DM）患者体内角膜基质环境的体外模型。

方法

从健康（HCFs）、1型糖尿病（T1DM）和2型糖尿病（T2DM）供体中分离人角膜成纤维细胞，并在维生素C刺激下培养4周，以促进细胞外基质（ECM）的分泌和组装。

结果

我们的数据表明，与HCFs相比，T1DM和T2DM的细胞形态发生改变，细胞迁移增加，ECM组装增加，且线粒体严重受损。此外，我们发现T1DM和T2DM中I型胶原蛋白和V型胶原蛋白的表达均显著下调。此外，还观察到纤维化标志物显著上调，包括T2DM中的α-平滑肌肌动蛋白以及T1DM和T2DM中的III型胶原蛋白。代谢分析表明糖酵解和三羧酸循环（TCA）途径受损。

结论

糖尿病对人角膜的生理和临床方面有显著影响。开发并全面表征我们的3D体外模型具有巨大益处，可能为新型治疗方法的开发提供线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a242/5179241/9dbeccdb0624/pone.0168845.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a242/5179241/c66a96e0f441/pone.0168845.g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a242/5179241/00f5f6325192/pone.0168845.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a242/5179241/181ed0041051/pone.0168845.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a242/5179241/15ccab1279ab/pone.0168845.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a242/5179241/1e35f3c27f90/pone.0168845.g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a242/5179241/c66a96e0f441/pone.0168845.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a242/5179241/633316a395a1/pone.0168845.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a242/5179241/fbed21b105d8/pone.0168845.g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a242/5179241/15ccab1279ab/pone.0168845.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a242/5179241/9dbeccdb0624/pone.0168845.g008.jpg

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