Polyethylene Glycol-Modified Pigment Epithelial-Derived Factor: New Prospects for Treatment of Retinal Neovascularization
| Autor: | Yujing Bai, Wenzhen Yu, Xiao-Lei Xu, Lvzhen Huang, Xiaoxin Li, Wei Du, Ai-Yi Zhou |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Angiogenesis Apoptosis Retinal Neovascularization Pharmacology Retina Polyethylene Glycols Neovascularization Mice chemistry.chemical_compound PEDF Cell Movement In vivo Human Umbilical Vein Endothelial Cells medicine Animals Humans Nerve Growth Factors Rats Wistar Eye Proteins Serpins Cell Proliferation Tube formation Neovascularization Pathologic business.industry Retinal medicine.disease Choroidal Neovascularization Recombinant Proteins eye diseases Rats Surgery Mice Inbred C57BL Choroidal neovascularization chemistry Molecular Medicine medicine.symptom business Retinopathy |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 342:131-139 |
| ISSN: | 1521-0103 0022-3565 |
| DOI: | 10.1124/jpet.112.192575 |
| Popis: | Pathological retinal neovascularization and choroidal neovascularization are major causes of vision loss in a variety of clinical conditions, such as retinopathy of prematurity, age-related macular degeneration, and diabetic retinopathy. Pigment epithelial-derived factor (PEDF) has been found to be the most potent natural, endogenous inhibitor of neovascularization, but its application is restricted because of its instability and short half-life. Polyethylene glycol (PEG) has been used as a drug carrier to slow clearance rate for decades. The present study investigated PEGylated-PEDF for the first time and evaluated its long-term effects on preventing angiogenesis in vitro and in vivo. PEG showed lower cytotoxicity to human umbilical vein endothelial cells (HUVECs). In vitro, PEGylated-PEDF inhibited HUVEC proliferation, migration, tube formation, and vascular endothelium growth factor secretion and induced HUVEC apoptosis in a dose-dependent manner, and it showed a statistically significant difference compared with the PEDF treatment group. In vivo, PEGylated-PEDF had a long-lasting effect in both plasma and retinal concentrations. In an oxygen-induced retinopathy model, one intravitreous injection of PEGylated-PEDF after mouse pups were moved into room air resulted in a significant difference in the inhibition of retinal neovascularization, which decreased the nonperfusion area, compared with the PEDF-treated group. Our present study demonstrated for the first time the long-term inhibitory effects of PEGylated-PEDF on the prevention of neovascularization in vitro and in vivo. These data suggest that PEGylated-PEDF could offer an innovative therapeutic strategy for preventing retinal neovascularization. |
| Databáze: | OpenAIRE |
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