Retinoprotective Effects of Moringa oleifera via Antioxidant, Anti-Inflammatory, and Anti-Angiogenic Mechanisms in Streptozotocin-Induced Diabetic Rats Suresh Kumar Gupta, 1 Binit Kumar, 1 B.P. Srinivasan, 1 Tapas Chandra Nag, 2 Sushma Srivastava, 1 Rohit Saxena, 3 and Ashutosh Aggarwal 1 Abstract Purpose: The present study was aimed to evaluate the retinoprotective effects of Moringa oleifera (MO) in Streptozotocin-induced diabetic rats. Methods: The study was continued for 24 weeks and evaluated for inflammatory (tumor necrosis factor [TNF]-a and interleukin [IL]-1b, angiogenic (vascular endothelial growth factor [VEGF] and protein kinase C [PKC]-b) and antioxidant (Glutathione, Superoxide dismutase, and Catalase) parameters. Retinal leakage was checked by Fluorescein angiography (FA) and fundus photographs were evaluated for retinal vessel caliber (arteriolar and venular). Transmission electron microscopy was done to determine basement membrane (BM) thickness. Results: The results of the present study showed potential hypoglycemic and retinal antioxidant effects of MO. In the present study, a significant rise in the expression of retinal inflammatory (TNF-a and IL-1b) and angio- genic (VEGF and PKC-b) parameters was observed in diabetic retinae as compared to normal retinae. However, MO-treated retinae showed marked inhibition in the expression of inflammatory and angiogenic parameters. Further, in the present study, diabetic retinae showed dilated retinal vessels as compared to normal. However, MO-treated retinae showed marked prevention in the dilatation of retinal vessels. Fluorescein angiograms obtained from diabetic retinae showed leaky and diffused retinal vasculature. On the other hand, MO-treated retinae showed intact retinal vasculature. Further, results of the transmission electron microscopy study showed thickened capillary BM in the diabetic retina as compared to normal retinae. However, treatment with MO prevented thickening of capillary BM. Conclusion: Our result suggests that MO may be useful in preventing diabetes induced retinal dysfunction. Introduction D iabetes is the disorder of metabolism and charac- terized by elevated blood glucose levels. This chronic uncontrolled hyperglycemic state leads to diabetic compli- cations, namely, Diabetic Neuropathy, Nephropathy, and Retinopathy. Diabetic retinopathy (DR) is one of the com- plications, which is characterized by morphological (leaky vessels) and structural alterations (capillary Basement membrane (BM) thickening, apoptosis, etc.) of retinal mi- crovasculature. Chronic hyperglycemic state is the major culprit, which leads to overproduction of reactive oxygen species (ROS) causing retinal oxidative stress. 1 Further, im- paired retinal antioxidant status leading to overexpression of proinflammatory (tumor necrosis factor [TNF]-a and inter- leukin (IL)-1b) and angiogenic (vascular endothelial growth factor [VEGF] and protein kinase C [PKC]-b) parameters, which are primarily responsible for the injured retinal mi- crovasculature. Proinflammatory parameters are highly re- sponsible for capillary endothelial cell apoptosis and increased BM thickness resulting in loss of pericytes. 2–4 As a result of all these pathological abnormal alterations leading to a hyperperfused retina 3 and the appearance of a new vessel in later stage. Moringa oleifera (MO) Lam (Family–Moringacea, also known as drumstick or horseradish tree) is a highly nutri- tious plant and consumed in many countries, particularly the Asian region (India, Pakistan), Hawaii, and many parts of 1 Ocular Pharmacology Laboratory, Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, University of Delhi, New Delhi, India. 2 Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India. 3 Dr. R.P. Center for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India. JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS Volume 29, Number 4, 2013 ª Mary Ann Liebert, Inc. DOI: 10.1089/jop.2012.0089 419 419 419