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M. A. Rosales, K. C. Silva, J. B. Lopes de Faria, J. M. Lopes de Faria; The Antioxidant Tempol Prevented the Early Markers of Diabetic Retinopathy in a Model That Combines Diabetes and Hypertension. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5904.
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© ARVO (1962-2015); The Authors (2016-present)
Hypertension is an important factor associated with development of diabetic retinopathy (DR). Oxidative pathways are proposed to explain how the hyperglycemia initiates the biochemical processes in the pathogenesis of DR. In the present study we sought to investigate if the antioxidant treatment with TEMPOL (mimetic of superoxide dismutase) prevents the early markers of DR in a model that combines diabetes and hypertension.
Four-week-old spontaneously hypertensive rats (SHR) were rendered diabetic by streptozotocin (60mg/kg). Diabetic SHR rats (DM SHR) were randomized for receive or not intraperitoneal injection of TEMPOL (250mg/kg/day). The normotensive Wystar Kyoto rats (WKY) were used as control group. After 20 days of diabetes, the rats were euthanized and the retinas collected.
The retinal expression of glial fibrillary acidic protein (GFAP) was increased in SHR group (p=0.001) and further more in DM SHR (p=0.0001). Extracellular matrix accumulation (ECM), evaluated by expression of fibronectin and collagen IV, revealed an increase in DM SHR compared with non diabetic groups (p=0.02). The oxidative status, evaluated by superoxide (O2-) and nitric oxide (NO) productions and the antioxidative reduced glutathione and extracellular superoxide dismutase, revealed an accentuated unbalance in favor to DM SHR rat, demonstrated by increase of O2- and NO productions (p= 0.04 and p=0.002, respectively) and decrease of the antioxidant systems (p=0.02). As a result, the product peroxynitrite detected by the "footprint" of nitrotyrosine, was higher in SHR group (p=0.008) and further increment was detected in DM SHR rats (p<0.0001). The treatment with TEMPOL reestablished all the above parameters.
Systemic administration of TEMPOL provides retinal protection against hyperglycemia and hypertension damages through the attenuation of peroxynitrite and improvement of the antioxidant system. These hypotheses suggest that TEMPOL, a catalytic antioxidant, may be used as a novel therapy for DR.
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