Upregulation of ASPP2 expression alleviates the development of proliferative vitreoretinopathy in a rat model.

AIM: To investigate whether upregulation of apoptosis-stimulating p53 protein 2 (ASPP2) expression could alleviate the development of proliferative vitreoretinopathy (PVR) in a rat model. METHODS: ASPP2-lentivirus or scrambled-lentivirus were transfected into ARPE-19 cells, followed with measurements of cell cytotoxicity by cell counting kit-8 assay. ASPP2 upregulation was confirmed by Western blotting and immunocytochemistry. Then ARPE-19 cells pretreated with ASPP2-lentivirus were intravitreally injected to Brown Norway rats to induce PVR models. PVR development and retinal function were evaluated by retinal photography and electroretinography, respectively. Finally, epithelial-mesenchymal transition as well as autophagy were investigated in rats' retinas via Western blotting. RESULTS: Protein expression of ASPP2 was significantly upregulated by ASPP2-lentivirus transfection in ARPE-19 cells. The development and progression of PVR were impeded significantly in rats with intravitreal injection of ARPE-19 cells pretreated with ASPP2-lentivirus. Accordingly, retinal functions were less affected and PVR grades were much lower in rats with ASPP2-lentivirus compared to scrambled-lentivirus treatment. Moreover, epithelial-mesenchymal transition and autophagy markers were decreased in the retinas of rats treated with ASPP2-lentivirus. CONCLUSION: ASPP2-lentivirus transfected to ARPE-19 cells mitigates the progression of PVR in rat models, which might be partly through reduced autophagy and attenuated epithelial-mesenchymal transition. ASPP2 might stand as a new approach for PVR treatment in the future.

Retraction Note to: A comparison of risk factors for age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese patients.

The article "A comparison of risk factors for age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese patients" has been retracted.

A comparison of risk factors for age-related macular degeneration and polypoidal choroidal vasculopathy in Chinese patients.

PURPOSE: Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are important vision-threatening diseases worldwide. For effective treatment, the risk factors for the diseases merit investigation. This study aimed to compare the risk factors for nAMD vs. PCV in Chinese patients. METHODS: A total of 946 participants were recruited in this case-control study, including 281 patients with nAMD, 306 patients with PCV, and 359 controls. All participants underwent comprehensive ophthalmic examinations. Information on risk factors were collected by questionnaire. Multivariate logistic regression analyses were performed to investigate the difference in risk factors between nAMD and PCV. In a subgroup of subjects, serum lipid data were obtained and analyzed. RESULTS: Risk factors for nAMD included older age (OR 1.03, P = 0.001), male gender (OR 1.55, P = 0.020), asthma (OR 2.50, P = 0.028), smoking (OR 1.92, P = 0.001), and family history (OR 6.82, P = 0.001), while smoking (OR 1.67, P = 0.013) was the only risk factor for PCV. Compared to patients with PCV, patients with nAMD were more likely to be older and suffer from hyperlipidemia, coronary artery disease, rheumatism, and tumor. Interestingly, higher levels of high-density lipoprotein were positively associated with PCV in the subgroup analysis (OR 7.74, P = 0.011). Besides, results were quite different between the combination of patients with nAMD and PCV and patients with nAMD or PCV alone. CONCLUSIONS: The risk factors for nAMD and PCV is varying with the exception of smoking. Our findings suggest that different strategies might be applied in the clinical management and scientific research on nAMD and PCV.

Inhibition of choroidal neovascularization by lentivirus-mediated PEDF gene transfer in rats.

AIM: To evaluate the effects of lentivirus-mediated pigment epithelium-derived factor (PEDF) gene transfer performed in treatment of rats with established choroidal neovascularization (CNV), and investigates the mechanism by which PEDF inhibits CNV in rats. METHODS: Brown Norway (BN) rats (n=204) were induced by exposure to a laser, and then randomly assigned to 3 groups: no treatment; treatments with intravitreal injection of lentivirus-PEDF-green fluorescent protein (GFP) or lentivirus-control GFP (free fluorescent protein). Following induction and treatment, the CNV tissue was assessed for form, size and vessel leakage by fluorescein fundus angiography (FFA), optical coherence tomography (OCT), histopathology, and examination of choroidal flat mounts. VEGF, Flk-1, and PEDF expression were evaluated by real-time polymerase chain reaction (PCR) and Western blot. RESULTS: A stable laser-induced rat model of CNV was successfully established, and used to demonstrate lentivirus-mediated PEDG gene transfer by intravitreal injection. Expression of green fluorescence labelled PEDF was observed in the retina up to 28d after injection. An intravitreal injection of lentivirus-PEDF-GFP at 7d led to a significant reduction in the size, thickness and area of CNV showed by FFA, OCT and choroidal flat mounts. PEDF was up-regulated while VEGF and Flk-1 were down-regulated in the lentivirus-PEDF-GFP group. The differences in VEGF and Flk-1 expression in the control and lentivirus-PEDF groups at 7, 14, 21 and 28d after laser induction were all statistically significant. CONCLUSION: Lentivirus-mediated PEDF gene transfer is effective for use in treatment of laser-induced CNV, and PEDF exerts its therapeutic effects by inhibiting expression of VEGF and Flk-1.

Neuroprotective effect of curcumin against oxidative damage in BV-2 microglia and high intraocular pressure animal model.

PURPOSE: The involvement of local and systemic oxidative stress in intraocular pressure (IOP) elevation and optic nerve damage has been hypothesized in the pathogenesis of glaucoma. In this study, we aim to evaluate the antioxidant effects of curcumin in BV-2 microglia oxidative damage and assess its neuroprotective effects in a chronic high IOP rat model. METHODS: BV-2 microglia cell line was used in an in vitro study and Wistar rats were used in an in vivo study. Cultured BV-2 microglia cells were pretreated with 10, 1, or 0.1 µM curcumin for 1 h, and sustained oxidative stress was induced by subjecting BV-2 microglia to 200 µM hydrogen peroxide (H2O2) for 24 h. MTT assay was used to determine cell viability. Changes of intracellular reactive oxygen species (ROS) and apoptosis were analyzed by flow cytometry. Three episcleral veins were cauterized to induce high IOP in Wistar rats and measured by Tonopen. After 6 weeks of treatment with curcumin (10 mg/kg/day) by intragastric administration, surviving of retinal ganglion cells was quantified. Activation of caspase 3, cytochrome c, BAX, and BCL2 was quantified by Western blotting both in BV-2 microglia and in animal model. Data were analyzed with the GraphPad Prism 5.0 software, and P<0.05 was considered to be statistically significant. RESULTS: The in vitro study showed that when BV-2 microglia was pretreated with curcumin, the cell viability increased and the intracellular ROS and apoptosis significantly decreased. In the in vivo study, chronic mild IOP elevation was induced for 4 weeks. In the curcumin-treated group, curcumin protected rat BV-2 microglia from death significantly. In both H2O2-treated BV-2 microglia and glaucoma models, caspase 3, cytochrome c, and BAX were downregulated and BCL2 was upregulated in the curcumin-treated group. CONCLUSIONS: Curcumin affords neuroprotective effects by inhibiting oxidative damage and could be a new or adjunctive treatment for glaucoma.