Inflammation affects the formation and the progression of various vitreoretinal diseases. We performed a comprehensive analysis of inflammatory immune mediators in the vitreous fluids from total of 345 patients with diabetic macular edema (DME, n = 92), proliferative diabetic retinopathy (PDR, n = 147), branch retinal vein occlusion (BRVO, n = 30), central retinal vein occlusion (CRVO, n = 13) and rhegmatogenous retinal detachment (RRD, n = 63). As a control, we selected a total of 83 patients with either idiopathic macular hole (MH) or idiopathic epiretinal membrane (ERM) that were free of major pathogenic intraocular changes, such as ischemic retina and proliferative membranes. The concentrations of 20 soluble factors (nine cytokines, six chemokines, and five growth factors) were measured simultaneously by multiplex bead analysis system. Out of 20 soluble factors, three factors: interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in all groups of vitreoretinal diseases (DME, PDR, BRVO, CRVO, and RRD) compared with control group. According to the correlation analysis in the individual patient's level, these three factors that were simultaneously increased, did not show any independent upregulation in all the examined diseases. Vascular endothelial growth factor (VEGF) was significantly elevated in patients with PDR and CRVO. In PDR patients, the elevation of VEGF was significantly correlated with the three factors: IL-6, IL-8, and MCP-1, while no significant correlation was observed in CRVO patients. In conclusion, multiplex bead system enabled a comprehensive soluble factor analysis in vitreous fluid derived from variety of patients. Major three factors: IL-6, IL-8, and MCP-1 were strongly correlated with each other indicating a common pathway involved in inflammation process in vitreoretinal diseases.

Cicatricial contraction of preretinal fibrous membrane is a cause of severe vision loss in proliferative vitreoretinal diseases such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). TGF-␤ is overexpressed in the vitreous of patients with proliferative vitreoretinal diseases and is also detectable in the contractile membranes. Therefore, TGF-␤ is presumed to contribute to the cicatricial contraction of the membranes, however, the underlying mechanisms and TGF-␤'s importance among various other factors remain to be elucidated. Vitreous samples from PDR or PVR patients caused significantly larger contraction of hyalocyte-containing collagen gels, compared with nonproliferative controls. The contractile effect was strongly correlated with the vitreal concentration of activated TGF-␤2 (r ‫؍‬ 0.82, P < 0.0001). proliferative diabetic retinopathy ͉ proliferative vitreoretinopathy ͉ fibrosis ͉ wound healing

Hyalocytes might be one of the critical components of ERM mediating its contractile property through the effect of TGF-beta2 in the vitreous fluid.

Subretinal injection of the dyes caused retinal cell degeneration at lower concentrations than those reported for intravitreous injection. However, subretinal injection of BBG at 0.25 mg/mL appeared to provide satisfactory biocompatibility.

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.RESEARCH DESIGN AND METHODS-Human vitreous concentrations of transforming growth factor-␤2 (TGF-␤2) were measured by enzyme-linked immunosorbent assay. TGF-␤2-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-␤2 were significantly higher in the samples from patients with PVD compared with those without PVD. Simvastatin inhibited TGF-␤2-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-␤2. 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.