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S. Kawahara, Y. Hata, T. Kita, R. Arita, M. Miura, S. Nakao, Y. Mochizuki, A. Ueno, A. Hafezi-Moghadam, T. Ishibashi; Potent Inhibition of Cicatricial Contraction in Proliferative Vitreoretinal Diseases by Statins. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5248. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Cicatricial contraction of preretinal proliferative membrane limits the surgical success for the treatment of proliferative vitreoretinal diseases such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). Novel pharmaceutical approaches are thus urgently needed for the management of these vision-threatening diseases. In this study, preventive effects of simvastatin, an inhibitor of HMG-CoA reductase, on the cicatricial contraction of proliferative membranes were examined.
Using cultured bovine hyalocytes, the inhibitory effects of simvastatin on transforming growth factor (TGF)-β2-dependent phosphorylation of myosin light chain (MLC) were analyzed by Western blotting. An in vitro type I collagen gel contraction assay was performed to evaluate the inhibitory effects of simvastatin on TGF-β2-dependent collagen gel contraction. The enhancements of MLC phophorylation and collagen gel contraction by exposing human vitreous samples were also evaluated. Furthermore, an experimental model of PVR was made in rabbit eyes, and the preventive effects of intravitreal application of simvastatin on the progression of PVR were examined.
Simvastatin inhibited TGF-β2-dependent phosphorylation of MLC and collagen gel contraction in a dose- and time-dependent manner. Human vitreous samples enhanced the phosphorylation state of MLC and collagen gel contraction, and the enhancements caused by the vitreous with PDR or PVR were larger than those caused by the vitreous with non-proliferative vitreoretinal disease. Simvastatin almost completely inhibited these enhancements. Finally, simvastatin significantly prevented the progression of PVR in rabbit eyes without apparent adverse effects.
These data indicated a novel therapeutic potential of simvastatin preventing cicatricial contraction of proliferative membranes in proliferative vitreoretinal diseases.
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