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Saffar Mansoor, Ramprasad Talahalli, Rose Gubitosi-Klug; Sex steroids and montelukast modulate hyperglycemia-induced retinal endothelial cell dysfunction. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5192.
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© ARVO (1962-2015); The Authors (2016-present)
Mouse models have suggested that sex steroids, perhaps through the generation of leukotrienes, may affect capillary degeneration, the hallmark feature of early diabetic retinopathy. This study investigates in vitro the mechanisms by which sex steroids (β-estradiol & testosterone) and the leukotriene receptor antagonist montelukast regulate hyperglycemia-induced retinal endothelial cell dysfunction
Mouse retinal endothelial cells (mREC) grown in hyperglycemic condition (25 mM) were chronically exposed to testosterone (T 10nM), b-estradiol (E 10nM) and Montelukast (M 1µM). Several critical parameters of retinal endothelial dysfunction were evaluated: superoxide generation, nitric oxide release, protein carbonyls production, antioxidant defense enzymes (catalase, SOD, glutathione peroxidase, glutathione transferase and glutathione reductase), endothelial cell permeability for FITC dextran using transwell inserts and cell viability by trypan blue exclusion method.
Under high glucose culture conditions, mREC treated with 10nM of testosterone had elevated levels of superoxide, nitric oxide and protein carbonyls (p<0.0001) compared to mREC treated with 10nM of estradiol and 1µM of montelukast. Activity of glutathione peroxidase and SOD, but not catalase and glutathione reductase, was higher in 10 nM testosterone treated cells (p<0.0001). Under hyperglycemic condition, in response to 10nM of testosterone treatment, the mREC permeability for FITC dextran was found to be significantly higher (p<0.0001) compared to cells treated with estradiol and montelukast. Elevated cell death (p<0.0001) was detected in testosterone treated cells when compared to estradiol and Montelukast treated cells under hyperglycemic conditions.
Estradiol at a physiologically relevant level may protect against hyperglycemia-induced retinal endothelial cell dysfunction. Similarly, montelukast may have beneficial antioxidant effects.
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