Potent inhibition of cicatricial contraction in proliferative vitreoretinal diseases by statins

Shuhei Kawahara, Yasuaki Hata, Takeshi Kita, Ryoichi Arita, Muneki Miura, Shintaro Nakao, Yasutaka Mochizuki, Hiroshi Enaida, Tadahisa Kagimoto, Yoshinobu Goto, Ali Hafezi-Moghadam, Tatsuro Ishibashi

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

OBJECTIVE-Despite tremendous progress in vitreoretinal surgery, certain postsurgical complications limit the success in the treatment of proliferative vitreoretinal diseases (PVDs), such as proliferative diabetic retinopathy (PDR) and proliferative vitreo-retinopathy (PVR). One of the most significant complications is the cicatricial contraction of proliferative membranes, resulting in tractional retinal detachment and severe vision loss. Novel pharmaceutical approaches are thus urgently needed for the management of these vision-threatening diseases. In the current study, we investigated the inhibitory effects of statins on the progression of PVDs. RESEARCH DESIGN AND METHODS-Human vitreous concentrations of transforming growth factor-β2 (TGF-β2) were measured by enzyme-linked immunosorbent assay. TGF-β2- and vitreous-dependent phosphorylation of myosin light chain (MLC), a downstream mediator of Rho-kinase pathway, and collagen gel contraction simulating cicatrical contraction were analyzed using cultured hyalocytes. Inhibitory effects of simva-statin on cicatrical contraction were assessed both in vitro and in vivo. RESULTS-Human vitreous concentrations of TGF-β2 were significantly higher in the samples from patients with PVD compared with those without PVD. Simvastatin inhibited TGF-β2- dependent MLC phosphorylation and gel contraction in a dose- and time-dependent manner and was capable of inhibiting translocation of Rho protein to the plasma membrane in the presence of TGF-β2. Vitreous samples from patients with PVD enhanced MLC phosphorylation and gel contraction, whereas simvastatin almost completely inhibited these phenomena. Finally, intravitreal injection of simvastatin dose-dependently prevented the progression of diseased states in an in vivo model of PVR. CONCLUSIONS-Statins might have therapeutic potential in the prevention of PVDs.

Original languageEnglish
Pages (from-to)2784-2793
Number of pages10
JournalDiabetes
Volume57
Issue number10
DOIs
Publication statusPublished - Oct 2008

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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