title: Polyethylene glycol-modified pigment epithelial-derived factor: new prospects for treatment of retinal neovascularization.
abstract: 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.
authors.affiliation: Key Laboratory of Vision Loss and Restoration, Ministry of Education, Department of Ophthalmology, Peking University People's Hospital, Xizhimen South Street 11, Xi Cheng District, 100044 Beijing, China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Bai
authors.forename: Lv-Zhen
authors.initials: LZ
authors.lastname: Huang
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: Ai-Yi
authors.initials: AY
authors.lastname: Zhou
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Yu
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000378:metabolism / Q000517:prevention & control; D005136:Eye Proteins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000517:prevention & control; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000097:blood / Q000235:genetics; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000378:metabolism; D015843:Serpins / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor