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Mallika Somayajulu, Sharon Ann McClellan, Sandamali Ekanayaka, Ahalya Pitchaikannu, Jena J Steinle, Linda D Hazlett; Diabetic Cornea: Effects of PM2.5 and glycyrrhizin treatment.. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4081.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the effects of fine particulate matter (PM2.5, diameter <2.5 µm), a major outdoor and indoor air pollutant worldwide and in Detroit, MI, in the diabetic cornea, and after treatment with glycyrrhizin (GLY).
In vitro, in vivo and ex vivo studies were done. An MTT assay tested cell viability of transformed human corneal epithelial cells (HCE-T) grown in 3D cultures under normal (5.5mM) and high (25mM) glucose levels with different concentrations (100, 200 and 500µg/ml) of the particulate. The effects of GLY on cell viability also were tested using the MTT assay. For in vivo studies, female C57BL/6 mice were made diabetic by injecting 60mg/kg of streptozotocin (STZ) dissolved in citrate buffer for up to 5 consecutive days. Control mice received citrate buffer only. A subset of the control and diabetic mice received GLY in their drinking water (150mg/kg/day) for 6 months. Mice were exposed topically to PM2.5 (400µg/5µl for 7d) and tested for levels of oxidative stress markers and pro-inflammatory molecules. For ex vivo studies, mRNA and protein levels of oxidative stress markers and pro-inflammatory molecules were measured from normal and diabetic corneas (all females; 50-71 years of age).
PM2.5 decreased cell viability in HCE-T grown in 3D culture under both normal and high glucose conditions and was concentration dependent. Toxic effects were seen only at 500µg/ml of PM2.5. In vivo, a significant increase in mRNA levels of pro-inflammatory and oxidative stress molecules was seen in the PBS versus GLY treated diabetic mouse cornea. Ex vivo studies using human corneas from diabetic patients showed that similar oxidative stress and pro-inflammatory molecules (seen in the mouse studies) were elevated when compared to normal age-matched controls. Additionally, HMGB1 and IL-1β protein levels were increased in diabetic vs normal human cornea.
Data provides evidence that PM2.5 exacerbates the effects of diabetes in the cornea. This is reflected in increased corneal stress, upregulation of markers of oxidative stress and innate immunity.
This is a 2020 ARVO Annual Meeting abstract.
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