Binit Kumar

Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic rats.

The purpose of the study was to evaluate the effects of hesperetin (Hsp) on diabetes-induced retinal oxidative stress, neuroinflammation and apoptosis in rats. The Hsp treatment (100 mg/kg body weight) was carried for twenty four weeks in STZ-induced diabetic rats and evaluated for antioxidant (Superoxide dismutase; SOD, Catalase; CAT and glutathione; GSH) enzymes, inflammatory cytokines (TNF-α, IL-1β), caspase-3, glial fibrillary acidic protein (GFAP) and aquaporin-4(AQP4) expression. Histological changes were evaluated by light and transmission electron microscopic (LM and TEM) studies. Retinal GSH levels and anti-oxidant enzymes (SOD and CAT) activity were significantly decreased in diabetic group as compared to normal group. However, in Hsp-treated rats, retinal GSH levels were restored close to normal levels and positive modulation of anti-oxidant enzyme activity was observed. Diabetic retinae showed significantly increased expression of Pro-inflammatory cytokines (TNF-α and IL-1β) as compared to normal retinae. While Hsp-treated retinae showed significantly lower levels of cytokines as compared to diabetic retinae. Diabetic retinae showed increased caspase-3, GFAP and AQP4 expression. However, Hsp-treated retinae showed inhibitory effect on caspase-3, GFAP and AQP4 expression. LM images showed edematous Müller cell endfeet, and also degenerated photoreceptor layer; however, protective effect of Hsp was seen on Müller cell processes and photoreceptors. TEM study showed increased basement membrane (BM) thickness in diabetic retina, while relatively thin BM was recorded in Hsp-treated retina. It can be postulated that dietary flavanoids, like Hsp, can be effective for the prevention of diabetes induced neurovascular complications such as diabetic retinopathy.

Green Tea Prevents Hyperglycemia-Induced Retinal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats

Purpose: Our objective was to investigate the effect of green tea (GT) on diabetes-induced retinal oxidative stress and proinflammatory parameters in rats. Methods: Treatment (200 mg/kg body weight) was carried out for a period of 16 weeks in streptozotocin-induced diabetic rats and was evaluated for hypoglycemic, antioxidant [reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)] and anti-inflammatory [tumor necrosis factor (TNF) α, vascular endothelial growth factor (VEGF)] activity. Histological changes were evaluated by transmission electron microscopy. Results: Retinal GSH levels were 1.5-fold lower in diabetic rats as compared to normal rats (p < 0.05). However, in GT-treated rats, retinal GSH levels were restored close to those of the normal group. The antioxidant enzymes SOD and CAT showed a more than 2-fold decrease in activity in diabetic retinae as compared to normal retinae (p < 0.05). Both SOD and CAT enzymatic activities were restored close to normal in the GT-treated group. Expression of proinflammatory parameters (TNF-α and VEGF) was significantly inhibited in GT-treated retinae as compared to diabetic retinae (p < 0.05). Moreover, GT treatment prevented retinal capillary basement membrane thickness. Conclusion: The beneficial effects of GT suggest its potential role in the prevention and treatment of diabetic retinopathy in human subjects.

Hesperetin ameliorates hyperglycemia induced retinal vasculopathy via anti-angiogenic effects in experimental diabetic rats.

The purpose of the study was to evaluate vasculoprotective effects of Hesperetin (Hsp) in Streptozotocin induced diabetic rats. The study was carried out for a period of 24weeks and evaluated for angiogenic parameters (VEGF and PKC-β), retinal vascular leakage by fluorescein angiography and, vessel (arteriolar and venular) diameters and any morphological abnormality through fundus photographs. Apart from this, transmission electron microscopy (TEM) was done to determine capillary basement membrane (BM) thickness. The results of the present study showed a significant increase in the expression of VEGF and PKC-β in diabetic retinae as compared to normal retinae. On the other hand, Hsp-treated retinae showed marked inhibition in the expression of VEGF and PKC-β. In the present study, diabetic retinae showed increase vascular permeability and leakage as compared to normal retinae. However, Hsp-treated retinae have not shown any such vascular dysfunctions. Moreover, there was significant increase in vessel caliber recorded in diabetic retinae compared to normal retinae, on the contrary Hsp-treated retinae showed lesser dilated vessels. Further, TEM study showed thickened BM in diabetic group as compared to normal group. However, Hsp-treated retinae showed marked prevention in BM thickness. In conclusion, it can be sated that Hsp has potential vasoprotective effects and can be useful in preventing diabetes induced vasculopathy.

Current trends in the pharmacotherapy of diabetic retinopathy

Diabetic retinopathy (DR) is one of the most debilitating disorders of microvasculature of the retina and one of the leading causes of vision loss among the working class worldwide. At present, intravitreal anti-inflammatory (corticosteroids) and anti-angiogenesis (anti-Vascular Endothelial Growth Factor) agents are being used as wide options for the pharmacotherapy of DR and diabetic macular edema (DME). Anti-inflammatory agents (Triamcinolone acetonide and other agents) have shown evidence-based clinical benefits in various randomized clinical trials for the treatment of DR and DME, and also shown improvement in best corrected visual acuity. However, direct intravitreal injections are associated with serious side-effects like cataract and elevation of Intra Ocular Pressure. Despite this, corticosteroid therapy has been effective for DR and DME, therefore current focus is on the development of novel intravitreal steroid delivery devices that release a small quantity over a prolonged period of time. In addition to corticosteroids, anti-angiogenic agents are found to be effective for the treatment of DR and DME. The most popular target of these agents is the subfamily of proteins known as VEGF, whose over-expression is believed to play a role in numerous diseases including DR and Age-related Macular Degeneration. Intravitreal bevacizumab (Avastin®) and Ranibizumab (Lucentis®) are gaining popularity as a clinical adjunct to panretinal photocoagulation in patients with proliferative DR. Moreover, Lucentis has been recently approved by the United States Food and Drug Administration for macular edema following retinal vein occlusion. Further, systemic agents (specially, hypoglycemic, hypolipidemic and anti-hypertensive agents) have shown beneficial results in reducing the progression of DR. In conclusion, it can be stated that for the present scenario systematic use of available pharmacotherapy as an adjunct to laser photocoagulation, which is gold standard therapy, can be a useful tool in the prevention of vision loss from DR and related disorders. This article summarizes the up-to-date developments in the pharmacotherapy of DR. Method- Literature search was done on online database, Pubmed, Google Scholar, clinitrials.gov and browsing through individual ophthalmology journals and leading pharmaceutical company websites.