Singapore Eye Research Institute, Singapore.
Invest Ophthalmol Vis Sci. 2011 Sep 27;52(10):7423-31. doi: 10.1167/iovs.11-7912.
To investigate the effect of tumor necrosis factor alpha (TNF-α) on the mouse retinal vasculature, function, and expression of vascular endothelial growth factor-A (VEGF-A) in the retina and retinal pigment epithelium (RPE) and to evaluate the protective effect of statin therapy (fluvastatin) on retinal vascular and functional changes.
A single intravenous injection of murine TNF-α (8 μg/kg body weight) was administered to one group of mice (TNF group). In the second group of mice (TNF+Statin group), a single dose of TNF-α was followed by 28 days oral medication of fluvastatin (10 mg/kg/d), and an equivalent volume of saline was administered to the third group (Control group). After 28 days, electroretinography (ERG) and fundus photography were performed. Eyes were collected for cell and molecular studies. Transcript levels of VEGF-A in retina and RPE were quantified using real-time polymerase chain reaction, and protein expression was analyzed by Western blot and immunostaining.
TNF-α-injected mice showed retinal vessel tortuosity, structural change, and altered retinal function. Fluvastatin-treated mice exhibited retinal vascular, structural, and functional changes almost similar to those of the control group. VEGF-A expression was significantly upregulated in the retina and RPE of TNF-α-injected mice, and this was significantly downregulated in fluvastatin-treated mice.
This study shows that the TNF-α-induced inflammatory process results in the alteration of retinal microvasculature and function, and fluvastatin could be a potential therapy for treating/preventing retinal microvascular or inflammatory complications.
研究肿瘤坏死因子-α（TNF-α）对小鼠视网膜血管、功能的影响，以及 TNF-α 在视网膜和视网膜色素上皮（RPE）中血管内皮生长因子-A（VEGF-A）的表达，并评估他汀类药物（氟伐他汀）治疗对视网膜血管和功能变化的保护作用。
一组小鼠（TNF 组）给予单次静脉注射鼠 TNF-α（8 μg/kg 体重）。第二组小鼠（TNF+Statin 组）在给予单次 TNF-α 后，给予 28 天氟伐他汀（10 mg/kg/d）口服治疗，第三组（对照组）给予等量生理盐水。28 天后进行视网膜电图（ERG）和眼底照相检查。收集眼球进行细胞和分子研究。使用实时聚合酶链反应定量检测 VEGF-A 在视网膜和 RPE 中的转录水平，并通过 Western blot 和免疫染色分析蛋白表达。
TNF-α 注射小鼠出现视网膜血管迂曲、结构改变和视网膜功能改变。氟伐他汀治疗的小鼠表现出的视网膜血管、结构和功能变化与对照组几乎相似。TNF-α 注射小鼠的视网膜和 RPE 中 VEGF-A 表达明显上调，而氟伐他汀治疗的小鼠中 VEGF-A 表达明显下调。
本研究表明，TNF-α 诱导的炎症过程导致视网膜微血管和功能改变，氟伐他汀可能是治疗/预防视网膜微血管或炎症并发症的潜在疗法。
