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Marlyn P Langford, Randa Eshaq, Thomas B Redens, Norman R Harris; Distribution of γ-glutamyltranspeptidase, aldose reductase, and biomarkers of oxidative stress in STZ-induced diabetic rat lens.. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2506.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate gamma-glutamyl transpeptidase (GGT, key to glutathione recapture and cell transformation), aldose reductase (AR, converts excess glucose to sorbitol) and oxidative stress markers, [8-OHdG (8-hydroxy-2’-deoxyguanosine, oxidized DNA marker) and annexin V (indicative of apoptosis)] expression in streptozotocin (STZ)-induced diabetic cataractous and normal rat lens.
Gross ocular examinations were performed and blood glucose levels were determined on adult control and diabetic [STZ-injected] Wistar rats. Bilateral eye enucleations were performed post euthanasia at 8 weeks and the eyes placed in 70% ethanol. Gross histopathology was determined on paraffin-embedded sections stained with hematoxylin and eosin. DAPI-treated sections were reacted with antibody to AR, GGT, 8-OHdG, and/or annexin V, the corneal and lens distributions were visualized using the immunofluorescent antibody method, and digital images captured for comparative analysis.
Gross cytopathological changes consistent with lens epithelial cells disorganization and sub-capsular lens fiber cell hyperplasia were noted in the cataractous lens of hyperglycemic STZ-injected rats. In control rat lens, GGT was prominently expressed by epithelial cells and diminished to undetectable levels within 1 mm (cortical zone) of the lens surface. GGT was not detected in the lens core of control rat lens. AR and oxidized DNA (8-OHdG) were detected in normal lens beneath the lens cortex within the lens fibers (1 mm from the surface) and core. Weak annexin V reactivity was detected in the lens epithelium. In the diabetic rat lens, GGT expression in epithelial cells was decreased, while GGT expression was increased on sub-capsular hyperplastic lens fiber cells. GGT was not detected in the diabetic lens nucleus. Increased AR expression and oxidized DNA (8-OHdG) were detected in the sub-capsular hyperplastic lens fiber cells of diabetic rat lens. Oxidized DNA was detected in annexin V-positive lens epithelial cells of some diabetic lenses.
The sub-capsular cataractogenic changes in STZ-induced hyperglycemic diabetic rats were associated with increased expression of AR and GGT with oxidized DNA-positive hyperplastic lens fiber cells. The results support hyperglycemia-induced lens fiber cell dedifferentiation and oxidative epithelial cell death as evidenced by annexin V expression.
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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