Verteporfin (VP), a light-activated drug used in photodynamic therapy for the treatment of choroidal neovascular membranes, has also been shown to be an effective inhibitor of malignant cells. Recently, studies have demonstrated that, even without photo-activation, VP may still inhibit certain tumor cell lines, including ovarian cancer, hepatocarcinoma and retinoblastoma, through the inhibition of the YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human glioma cell lines (LN229 and SNB19). Through western blot analysis, we identified that human glioma cells that were exposed to VP without light activation demonstrated a downregulation of YAP-TEAD-associated downstream signaling molecules, including c-myc, axl, CTGF, cyr61 and survivin and upregulation of the tumor growth inhibitor molecule p38 MAPK. In addition, we observed that expression of VEGFA and the pluripotent marker Oct-4 were also decreased. Verteporfin did not alter the Akt survival pathway or the mTor pathway but there was a modest increase in LC3-IIB, a marker of autophagosome biogenesis. This study suggests that verteporfin should be further explored as an adjuvant therapy for the treatment of glioblastoma.

PurposeThe purpose of this study was to develop a method for isolating, culturing, and characterizing cells from patient-derived membranes in proliferative vitreoretinopathy (PVR) to be used for drug testing.MethodsPVR membranes were obtained from six patients with grade C PVR. Membrane fragments were analyzed by gross evaluation, fixed for immunohistologic studies to establish cell identity, or digested with collagenase II to obtain single cell suspensions for culture. PVR-derived primary cultures were used to examine the effects of methotrexate (MTX) on proliferation, migration, and cell death.ResultsGross analysis of PVR membranes showed presence of pigmented cells, indicative of retinal pigment epithelial cells. Immunohistochemistry identified cells expressing α-smooth muscle actin, glial fibrillary acidic protein, Bestrophin-1, and F4/80, suggesting the presence of multiple cell types in PVR. Robust PVR primary cultures (C-PVR) were successfully obtained from human membranes, and these cells retained the expression of cell identity markers in culture. C-PVR cultures formed membranes and band-like structures in culture reminiscent of the human condition. MTX significantly reduced the proliferation and band formation of C-PVR, whereas it had no significant effect on cell migration. MTX also induced regulated cell death within C-PVR as assessed by increased expression of caspase-3/7.ConclusionsPVR cells obtained from human membranes can be successfully isolated, cultured, and profiled in vitro. Using these primary cultures, we identified MTX as capable of significantly reducing growth and inducing cell death of PVR cells in vitro.

Purpose To characterize the development of retinal detachment after open globe trauma. Design Case-control study Participants 892 patients comprising 893 open globe injuries, of which 255 were ultimately diagnosed with retinal detachment, with the remaining eyes serving as controls. Methods Retrospective chart review of open globe injuries presenting to the Massachusetts Eye and Ear Infirmary between 1999 and 2011. Kaplan-Meier analysis was used to estimate time to detachment and multivariable logistic regression was used to define clinical factors associated with retinal detachment after open globe injury. Main Outcome Measures Demographic and clinical characteristics at the time of presentation after open globe injury, date of retinal detachment diagnosis, and last date of follow-up. Results Primary repair of the open globe was typically undertaken within hours of presentation. 255 eyes were ultimately diagnosed with retinal detachment after open globe trauma, yielding an incidence of 29% (95% confidence interval: 26%-32%). For eyes that developed retinal detachment, 27% (69/255) detached within 24 hours of primary open globe repair, 47% (119/255) detached within one week, 72% (183/255) within one month. Multivariable regression analysis revealed presence of vitreous hemorrhage (odds ratio: 7.29, p<0.001), higher zone of injury (odds ratio: 2.51 per integer increase in zone number, odds ratio: 1.00-6.30, p<0.001), and poorer Logarithm of the Minimum Angle of Resolution visual acuity at the time of presentation after open globe injury (odds ratio: 2.41 per integer increase in Logarithm of the Minimum Angle of Resolution visual acuity, odds ratio: 1.00-81.30, p<0.001) to be associated with retinal detachment. A screening tool, named herein the Retinal Detachment after Open Globe Injury (RD-OGI) score, was created. Conclusions Retinal detachment is common after open globe trauma, though often not appearing until days to weeks after the initial traumatic event. Several clinical variables at the time of initial presentation can predict the future risk of detachment.