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Mohammad Ola, Mohd Nawaz, Hatem Abuohashish, Abdullah Alhomaida, Salim Al-Rejai, Mohammed Ahmed; Telmisartan increases the levels of brain derived neurotrophic factor and glutathione in the retina of streptozotocin-induced diabetic rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2694.
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© ARVO (1962-2015); The Authors (2016-present)
Activation of renin angiotensin system (RAS) is one of the key pathophysiological processes in diabetic retinopathy. Increase in the expression of angiotensin II type 1 receptor (AT1R) in diabetic retina has been shown to play a pivotal role in damaging neuronal component of retina, a widely recognized early feature of diabetic retinopathy. The purpose of this study is to determine the effect of telmisartan, an AT1R blocker on amelioration of reduced neurotrophic support and antioxidant status in the diabetic rat retina.
Diabetes was induced by streptozotocin (STZ) in the male Wister rats. Three weeks of diabetic rats were orally treated with telmisartan (10 mg/kg/d) for 4 weeks, and then serum and retina collected for the analyses and compared with their age matched non-diabetic control and untreated diabetic rats. The levels of brain derived neurotrophic factor (BDNF) in the serum and retina of non-diabetic, diabetic and telmisartan treated diabetic rats were measured by ELISA and glutathione by biochemical methods. The expression of BDNF and ciliary neurotrophic factor (CNTF) in retinal samples were analyzed by immunoblotting techniques. The caspase-3 activity in the retinal tissue was measured using a caspase-3 colorimetric assay kit.
The level of BDNF in the serum and retina of telmisartan treated diabetic rats were found to be significantly increased compared to untreated diabetic rats: (serum, 1.33 ± 0.14 to 1.82 ± 0.25 ng/ml ; retina,16.36 ± 2.0 to 22.00 ± 2.5 pg/ml, p< 0.05). Glutathione level was increased both in the serum and retina of drug treated diabetic rats: (serum, 0.70 ± 0.07 to 0.90 ± 0.08 μM; retina, 2.27 ± 0.11 to 3.2 ± 0.45 μM/μg protein, p<0.05). The caspase-3 activity in the diabetic treated retina was significantly decreased to control level. The protein expression levels of BDNF and CNTF were increased significantly in the drug treated diabetic rat retinas compared to untreated diabetic rats.
AT1R blocker telmisartan increased the neurotrophic support and endogenous antioxidant glutathione both systemically and locally in the diabetic retina, and decreased signs of apoptosis in the diabetic retina, suggesting its potential role as a neuroprotective agent in diabetic retinopathy.
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