Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves mult...Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves multiple molecular pathways and is characterized chronic neurovascular degeneration. Current approaches to prevent or to treat DR are still far from satisfactory. Therefore, it is important to develop new therapeutic strategies for the prevention and treatment to DR. Pigment epithelium-derived factor (PEDF), a 50-kDa secreted glycoprotein, has been described as a multi-functional protein. Some emerging evidences indicate that PEDF are able to target multiple pathways exerting neurotropic, neuroprotective, anti-angiogenic, antivasopermeability, anti-inflammation, anti-thrombogenic and anti-oxidative effects in DR. In this review, we addressed the functions of PEDF in different pathways, which could lead to potential therapeutics on the treatment to DR.展开更多
Pigment epithelium derived factor (PEDF) has been proven to be an effective drug for the treatment of choroidal neovascularization (CNV).However,the lack of ideal administration route is the biggest bottleneck prevent...Pigment epithelium derived factor (PEDF) has been proven to be an effective drug for the treatment of choroidal neovascularization (CNV).However,the lack of ideal administration route is the biggest bottleneck preventing PEDF from wider clinical use.In this study,we developed a novel PEDF-carrying system which employed immuno-nano-liposomes (INLs) under ultrasound exposure.PEDF-loaded INLs were prepared by conjugating nanoliposomes to the peptide ATWLPPR specifically targeting the receptor-2 for vascular endothelial growth factor (VEGFR-2) and reversely encapsuling PEDF.RF/6A cells were incubated with PEDF-loaded INLs.CNV models of BN rats were injected with PEDF-loaded INLs.MTT assay was used to evaluate the cytotoxicity of the INLs on RF/6A cells.Flow cytometry was conducted to detect the apoptotic rate of cells.Laser scanning confocal microscopy was employed to observe the binding and transmitting process of PEDF-loaded INLs and to calculate the area of CNV in the rat model.The results showed that the PEDF-loaded INLs could exclusively bind to CNV but not to the normal choroidal vessels.The CNV area was significantly decreased in PEDF treatment groups in comparison with control group (P【0.05).Moreover,PEDF-loaded INLs exposed under ultrasound were more efficient in reducing the CNV area (P【0.05).It was concluded that INLs in combination with ultrasonic exposure can transmit PEDF into cytoplasma with high specificity and efficiency,which strengthens the inhibitory effects of PEDF on CNV and reduces its side effects.PEDF-loaded INLs possibly represent a new treatment paradigm for patients with ocular neovascularization.展开更多
文摘Diabetic retinopathy (DR), a major micro-vascular complication of diabetes, has emerged as a leading cause of visual impairment and blindness among working adults in the worldwide. The pathobiology of DR involves multiple molecular pathways and is characterized chronic neurovascular degeneration. Current approaches to prevent or to treat DR are still far from satisfactory. Therefore, it is important to develop new therapeutic strategies for the prevention and treatment to DR. Pigment epithelium-derived factor (PEDF), a 50-kDa secreted glycoprotein, has been described as a multi-functional protein. Some emerging evidences indicate that PEDF are able to target multiple pathways exerting neurotropic, neuroprotective, anti-angiogenic, antivasopermeability, anti-inflammation, anti-thrombogenic and anti-oxidative effects in DR. In this review, we addressed the functions of PEDF in different pathways, which could lead to potential therapeutics on the treatment to DR.
基金supported by a grant from National Natural Sciences Foundation of China(No.30600691,30811260207)
文摘Pigment epithelium derived factor (PEDF) has been proven to be an effective drug for the treatment of choroidal neovascularization (CNV).However,the lack of ideal administration route is the biggest bottleneck preventing PEDF from wider clinical use.In this study,we developed a novel PEDF-carrying system which employed immuno-nano-liposomes (INLs) under ultrasound exposure.PEDF-loaded INLs were prepared by conjugating nanoliposomes to the peptide ATWLPPR specifically targeting the receptor-2 for vascular endothelial growth factor (VEGFR-2) and reversely encapsuling PEDF.RF/6A cells were incubated with PEDF-loaded INLs.CNV models of BN rats were injected with PEDF-loaded INLs.MTT assay was used to evaluate the cytotoxicity of the INLs on RF/6A cells.Flow cytometry was conducted to detect the apoptotic rate of cells.Laser scanning confocal microscopy was employed to observe the binding and transmitting process of PEDF-loaded INLs and to calculate the area of CNV in the rat model.The results showed that the PEDF-loaded INLs could exclusively bind to CNV but not to the normal choroidal vessels.The CNV area was significantly decreased in PEDF treatment groups in comparison with control group (P【0.05).Moreover,PEDF-loaded INLs exposed under ultrasound were more efficient in reducing the CNV area (P【0.05).It was concluded that INLs in combination with ultrasonic exposure can transmit PEDF into cytoplasma with high specificity and efficiency,which strengthens the inhibitory effects of PEDF on CNV and reduces its side effects.PEDF-loaded INLs possibly represent a new treatment paradigm for patients with ocular neovascularization.
