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Effect of N ‐acetylcysteine on the early expression of inflammatory markers in the retina and plasma of diabetic rats
Author(s) -
Tsai Gina Y,
Cui Jing Z,
Syed Husnain,
Xia Zhengyuan,
Ozerdem Ugur,
McNeill John H,
Matsubara Joanne A
Publication year - 2009
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/j.1442-9071.2009.02000.x
Subject(s) - medicine , oxidative stress , pericyte , inflammation , diabetic retinopathy , streptozotocin , pathogenesis , endocrinology , vascular endothelial growth factor , retinal , tumor necrosis factor alpha , superoxide dismutase , diabetes mellitus , endothelial stem cell , chemistry , biochemistry , ophthalmology , vegf receptors , in vitro
A bstract Purpose: The aim of this study is to investigate markers of inflammation and oxidative stress in an early model of diabetic retinopathy, correlate retinal and plasma results and evaluate the influence of treatment by N ‐acetylcysteine (NAC), a free radical scavenger. Methods: Four groups were studied: control (C), streptozotocin (STZ)‐induced diabetic rats (D), STZ rats following 8 weeks of NAC (DT), and control rats following 8 weeks of NAC (CT). Plasma levels of free 15‐F2t‐isoprostane (15‐F‐2t‐IsoP), superoxide dismutase (SOD) and tumour necrosis factor‐alpha (TNF‐α) were obtained. Primary antibodies against macrophages (ED‐1), microglia (Ox‐42), pericytes (NG‐2), endothelial and perivascular cells (IB‐4), haem oxygenase 1 (HO‐1) and vascular endothelial growth factor (VEGF) were used. Results: Expression of NG‐2 was robust in C, CT, DT, and mild in D. The intensity of IB‐4 was higher in D and DT compared with the C and CT. Ox‐42 and ED‐1 expression was higher in the D than in the DT, C or CT. Expression of VEGF and HO‐1 was non‐specific across the four groups. Plasma levels of 15‐F‐2t‐IsoP and TNF‐α were higher in the D as compared with the C, CT and DT. SOD levels were lower in the D when compared with the C, CT and D. Conclusions: Macrophage/microglia activation, pericyte loss and endothelial/perivascular cell changes occur early in the pathogenesis of DR. These changes are associated with an increase in plasma markers of oxidative stress and inflammation and are minimized by treatment with NAC. The results suggest that therapies that reduce free radicals will help minimize the early events in diabetic retinopathy in the STZ model.