title: Inhibition of Pterygium Fibroblast Migration and Outgrowth by Bevacizumab and Cyclosporine A Involves Down-Regulation of Matrix Metalloproteinases-3 and -13.
abstract: We examined the connection between matrix metalloproteinase (MMP) expression/activity and pterygium fibroblast migration, and how these were affected by bevacizumab and/or cyclosporine A (CsA). Fibroblasts were obtained from 20 pterygia and 6 normal conjunctival specimens. Expression levels of MMP-3 and MMP-13 were examined after bevacizumab administration. Immunofluorescence staining was used to examine expression of both MMPs in fibroblasts migrating out from explanted pterygium tissues. Rates of cell migration from explant-cultured pterygia tissues and scratch-wounded confluent pterygium fibroblasts were examined in the presence of MMP-3 or MMP-13 inhibitors, as well as bevacizumab and/or CsA. A scratch wound healing migration assay was performed to determine the effects of bevacizumab and/or CsA. Protein expression of both MMPs in pterygium tissues and in cells migrating from organ-cultured pterygium tissues was greater than that observed in normal cells. Inhibition of the activities of both MMPs decreased their expression levels; these were also significantly reduced in bevacizumab-injected pterygium tissues. Bevacizumab significantly reduced the expression of both MMPs and cell migration. Pretreatment with CsA prior to bevacizumab exposure markedly inhibited cell migration and the expression of both MMPs. CsA enhanced the inhibitory effects of bevacizumab on pterygium fibroblast migration in vitro, possibly by inhibiting expression of both MMPs. These findings suggest that combined CsA and bevacizumab treatment may provide a potential therapeutic strategy for reducing the rate of pterygium recurrence.
authors.affiliation: Cheil Eye Research Institute, Cheil Eye Hospital, 1 Ayang-Ro, Dong-Gu, Daegu, Republic of Korea.|Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Cheomdan-ro Dong-gu, Daegu, Republic of Korea.
authors.forename: Yeoun-Hee
authors.identifier: http://orcid.org/0000-0002-2815-5886
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Jae-Chang
authors.initials: JC
authors.lastname: Jung
authors.affiliation: Cheil Eye Research Institute, Cheil Eye Hospital, 1 Ayang-Ro, Dong-Gu, Daegu, Republic of Korea.
authors.forename: Sang Il
authors.initials: SI
authors.lastname: Gum
authors.affiliation: Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Su-Bin
authors.initials: SB
authors.lastname: Park
authors.affiliation: Korean Medicine (KM)-Application Center, Korea Institute of Oriental Medicine (KIOM), Cheomdan-ro Dong-gu, Daegu, Republic of Korea.
authors.forename: Jin Yeul
authors.initials: JY
authors.lastname: Ma
authors.affiliation: Cheil Eye Research Institute, Cheil Eye Hospital, 1 Ayang-Ro, Dong-Gu, Daegu, Republic of Korea.
authors.forename: Yong Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Cheil Eye Research Institute, Cheil Eye Hospital, 1 Ayang-Ro, Dong-Gu, Daegu, Republic of Korea.
authors.forename: Kyoo Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Cheil Eye Research Institute, Cheil Eye Hospital, 1 Ayang-Ro, Dong-Gu, Daegu, Republic of Korea.
authors.forename: Young Jeung
authors.identifier: http://orcid.org/0000-0001-8959-4033
authors.initials: YJ
authors.lastname: Park
mesh_terms: D000068258:Bevacizumab / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D016572:Cyclosporine / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D011625:Pterygium / Q000378:metabolism*
chemical_list: D000068258:Bevacizumab; D016572:Cyclosporine; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3