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SHIRISH Satish DONGARE, Suresh Kumar Gupta, Rajani Mathur, Rohit Saxena, Sushma Srivastava, Tapas C Nag; Genistein ameliorates diabetic retinopathy by suppression of oxidative stress, inflammation and angiogenic markers in streptozotocin induced retinal neovascularization in neonatal rats (nSTZ).. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):175.
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© ARVO (1962-2015); The Authors (2016-present)
This study evaluates effect of isoflavone Genistein (300 mg/kg/day, po) on retinal oxidative stress, inflammation and neovascularization in nSTZ.
Streptozotocin (STZ 90mg/kg; i.p.) was administrated to two days old rat pups and six weeks later fasting glucose level (FGL) was checked. Animals with FGL ≥ 160 mg/dl were identified as diabetic and included in study that was carried out for 24 weeks. The diabetic animals were randomly divided into two groups (n=16) diabetic control (DC) and genistein treated (Gnst) and data was compared against age matched normal animals (NC). The animals were evaluated for retinal total antioxidant capacity (TAC), Tumor Necrosis Factor-α (TNF-α), vascular endothelial growth factor (VEGF), vessel abnormalities, vascular leakage, Immunohistochemistry also performed for nuclear factor kappa B (NF-kB) and caspase-3. Ultra-structural changes were evaluated by transmission electron microscopic (TEM) studies.
TAC level of retinas were significantly decreased in DC as compared to NC whereas, Gnst protected against depletion of TAC level. A significant rise in the levels of VEGF and TNF-α in DC (16.20±3.28 & 71.90±10.24 pg/ml, respectively) was observed as compared to NC (6.45±2.18 & 29.82±3.38 pg/ml, respectively) however, it was significantly reduced in Gnst (9.32±2.10 & 38.70±9.83 pg/ml, respectively). Diameters of retinal arterioles and venules were significantly increased in DC retinas as compared to NC but, restored in Gnst retinal vessels. Fundus fluorescein angiograms from DC showed increased retinal vascular permeability and leakage, that was absent in Gnst. Retinal immunoreactivity (NF-kB and caspase-3) was raised in DC compared to the other groups. TEM observation revealed thickened BM (0.23±0.04 µm) in DC as compared to NC (0.07±0.01 µm) but, comparatively thin in Gnst (0.16±0.02 µm).
The results of the present study demonstrate that Genistein protects against retinal oxidative stress, inflammation and angiogenesis in streptozotocin induced retinal neovascularization in neonatal rats.
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