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Remya Robinson, Chi Luu, Moe K. Thu, Queenie Tan, Tien Y. Wong, Barathi A. Veluchamy; TNF- α Induced Retinal Vessel Tortuosity and Protective Effect of Fluvastatin Through Down Regulation of VEGF-a Receptors. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3342.
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To investigate retinal microvascular changes and function in Tumor Necrosis Factor α (TNF-α) induced mouse model, to determine the gene expression of Vascular Endothelial growth factor-a (VEGF-a) receptors in the retina and the protective effect of fluvastatin treatment.
A single dose of murine TNF-α (8µg/kg body weight) was given to one group of C57BL6/J mice via intravenous injection. Control group of mice was injected with an equivalent volume of saline. In the 2nd group, single intravenous injection of TNF-α was followed by 6weeks oral medication of fluvastatin (10mg/Kg/day) (n=18 mice in each group). Fundus photography and Fundus Fluorescein Angiography (FFA) was performed using Kowa Genesis small animal fundus. Dark-adapted Electroretinography (ERG) was recorded with Espion system. Both FFA and ERG were performed at 28 days and 42 days in all 3 groups of mice to examine the retinal vascular changes and function respectively. Gene expression of VEGF-a receptors was studied using RT-qPCR to determine their role in TNF-α induced microvascular complications and in the protective effect of fluvastatin. VEGF-a receptor protein expression was detected by western blotting.
FFA of TNF-α injected mice showed retinal vessel tortuosity where as fluvastatin treated mice exhibited no vessel tortuosity. Abnormal ERG recordings were observed in the TNF-α injected group as compared to control indicating alterations in retinal function. ERG recordings were near to control in the fluvastatin treated group. RT-qPCR studies showed significant up regulation (p<0.05) of VEGF-a receptor gene expression in the retina of TNF-α injected group and this was significantly (p<0.05) down regulated to near control in fluvastatin treated group. Western blotting studies of VEGF-a receptor showed protein expression to be as well.
TNF-α can induce retinal vessel tortuosity, which is suggested to be mediated through increased expression of VEGF-a receptors. Fluvastatin therapy can reverse TNF-α induced retinal vessel tortuosity by down regulation of VEGF-a receptors. Our findings indicate that fluvastatin might have an anti-VEGF activity and it could be a potential drug for treating retinal micro-vascular related complications.
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