Fluvastatin downregulates VEGF-A expression in TNF-α-induced retinal vessel tortuosity.

PURPOSE: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.