title: Inhibition of corneal neovascularization with the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18) vector in a rat corneal experimental angiogenesis model.
abstract: Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18) has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and D: 10 μg + 10 μg) of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 μgof p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV.The bFGF and PEDF genes were successfully expressed as shown by western blot analysis,and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival bevacizumab administration combined with a relatively safe profile and low toxicity.
authors.affiliation: Department of Ophthalmology, Chang Gung Memorial Hospital, No.6, W. Sec., Jiapu Rd., Puzi City, Chiayi County 61363, Taiwan. chench@mail.ncyu.edu.tw.
authors.forename: Chien-Neng
authors.initials: CN
authors.lastname: Kuo
authors.forename: Chung-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: San-Ni
authors.initials: SN
authors.lastname: Chen
authors.forename: Lin-Cheng
authors.initials: LC
authors.lastname: Yang
authors.forename: Li-Ju
authors.initials: LJ
authors.lastname: Lai
authors.forename: Chien-Hsiung
authors.initials: CH
authors.lastname: Lai
authors.forename: Miao-Fen
authors.initials: MF
authors.lastname: Chen
authors.forename: Chia-Hui
authors.initials: CH
authors.lastname: Hung
authors.forename: Ching-Hsein
authors.initials: CH
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D000068258:Bevacizumab; D016510:Corneal Neovascularization / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011726:Pyridinium Compounds / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D013501:Surface-Active Agents / Q000008:administration & dosage; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005136:Eye Proteins; D016222:Fibroblast Growth Factor 2; D009414:Nerve Growth Factors; D011726:Pyridinium Compounds; D011994:Recombinant Proteins; D015843:Serpins; D013501:Surface-Active Agents; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C532953:1-methyl-4-(9-dioleyl)methylpyridinium; C467498:vascular endothelial growth factor A, rat