title: VEGF-binding aptides and the inhibition of choroidal and retinal neovascularization.
abstract: Age-related macular degeneration and diabetic retinopathy are leading causes of blindness. Vascular endothelial growth factor (VEGF) is known to be the main factor that induces pathological angiogenesis in these diseases. In this study, we investigate the therapeutic potential and safety profiles of high-affinity peptides targeting VEGF which are identified using an 'aptide' technology. We show that two VEGF-binding aptides, APTVEGF1 and APTVEGF2, demonstrate high binding affinity and specificity to VEGF. Furthermore, they suppress VEGF-induced activation of VEGF receptor-2, in vitro angiogenesis, and in vivo pathological choroidal and retinal neovascularization. Despite potent anti-angiogenic effects, both VEGF-binding aptides do not induce any definite toxicity at the level of cellular viability, histological integrity, and gene expression. Our data show the therapeutic potential of VEGF-binding peptides for the treatment of choroidal and retinal neovascularization.
authors.affiliation: Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea; Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea. Electronic address: steph25@snu.ac.kr.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Jo
authors.affiliation: KAIST Institute of the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Sunghyun
authors.initials: S
authors.lastname: Kim
authors.affiliation: KAIST Institute of the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Daejin
authors.initials: D
authors.lastname: Kim
authors.affiliation: Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Kim
authors.affiliation: KAIST Institute of the BioCentury, Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea. Electronic address: syjon@kaist.ac.kr.
authors.forename: Sangyong
authors.initials: S
authors.lastname: Jon
authors.affiliation: Fight against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Republic of Korea; Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul 110-799, Republic of Korea; Department of Ophthalmology, College of Medicine, Seoul National University, Seoul 110-744, Republic of Korea.
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use* / Q000633:toxicity; D011485:Protein Binding; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism* / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Age-related macular degeneration; Choroidal neovascularization; Diabetic retinopathy; Pathological angiogenesis; Retinal neovascularization; Vascular endothelial growth factor