Abstract
PurposeTo establish an in vitro model that would mirror the in vivo corneal stromal environment in diabetes (DM) patients.MethodsHuman 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.ResultsOur 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.ConclusionDM 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.
Highlights
Diabetes mellitus (DM) is a common metabolic disease characterized by hyperglycemic condition that has a higher prevalence rate with increased number of cases every year[1,2]
We have developed a stroma-like model that consists of primary human corneal fibroblasts from healthy (HCF), Type 1DM (T1DM), and Type 2DM (T2DM) donors that can mimic the stroma seen in vivo
We extended our expertise to develop those 3D constructs using T1DM and T2DM primary human corneal cells
Summary
Diabetes mellitus (DM) is a common metabolic disease characterized by hyperglycemic condition that has a higher prevalence rate with increased number of cases every year[1,2]. 371 million people have been diagnosed with DM worldwide and the incidence rate is expected to double by 2030[3,4,5]. In the United States it has been termed as the epidemic disease of an increasing age and obese population[1]. 6.2 million people are underdiagnosed in the United States alone. T1DM is known as “insulin dependent” or “juvenile-onset’ diabetes and caused due to the autoimmune destruction of the β-cells in the pancreas, accounting for about 5–10% of total DM cases worldwide[2,5,6]. T2DM accounts for about ~90–95% of total DM population [2,5,6]
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