title: Potent inhibition of cicatricial contraction in proliferative vitreoretinal diseases by statins.
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 vitreoretinopathy (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.
  
  
  METHODS
  Human vitreous concentrations of transforming growth factor-beta2 (TGF-beta2) were measured by enzyme-linked immunosorbent assay. TGF-beta2-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 simvastatin on cicatrical contraction were assessed both in vitro and in vivo.
  
  
  RESULTS
  Human vitreous concentrations of TGF-beta2 were significantly higher in the samples from patients with PVD compared with those without PVD. Simvastatin inhibited TGF-beta2-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-beta2. 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.
authors.affiliation: Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Maidashi, Higashi-Ku, Fukuoka, Japan.
authors.forename: Shuhei
authors.initials: S
authors.lastname: Kawahara
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Hata
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kita
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Arita
authors.forename: Muneki
authors.initials: M
authors.lastname: Miura
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nakao
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Mochizuki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Enaida
authors.forename: Tadahisa
authors.initials: T
authors.lastname: Kagimoto
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Goto
authors.forename: Ali
authors.initials: A
authors.lastname: Hafezi-Moghadam
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D015153:Blotting, Western; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000517:prevention & control; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D046529:Microscopy, Electron, Transmission; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D019821:Simvastatin / Q000494:pharmacology*; D053781:Transforming Growth Factor beta2 / Q000378:metabolism*; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism / Q000517:prevention & control; D014822:Vitreous Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D000960:Hypolipidemic Agents; D018994:Myosin Light Chains; D053781:Transforming Growth Factor beta2; D003094:Collagen; D019821:Simvastatin; D020741:rho GTP-Binding Proteins