title: Periostin promotes the generation of fibrous membranes in proliferative vitreoretinopathy.
abstract: Proliferative vitreoretinopathy (PVR) is a severe, vision-threatening disorder characterized by the fibrous membrane formation that leads to tractional retinal detachment. There has been no effective therapeutic approach other than vitreoretinal surgery. In this study, DNA microarray analysis of the fibrous membranes revealed significant up-regulation of periostin. We also found increased periostin expression in the vitreous and retinal pigment epithelial (RPE) cells from fibrous membranes of PVR patients. In vitro, periostin increased proliferation, adhesion, migration, and collagen production in RPE cells through integrin αV-mediated FAK and AKT phosphorylation. Periostin blockade suppressed migration and adhesion induced by TGFβ2 and PVR vitreous. In vivo, periostin inhibition had the inhibitory effect on progression of experimental PVR in rabbit eyes without affecting the viability of retinal cells. These results identified periostin as a pivotal molecule for fibrous membrane formation as well as a promising therapeutic target for PVR.
authors.affiliation: 1Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, 812-8582, Japan. yosida@eye.med.kyushu-u.ac.jp.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yoshida
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nakao
authors.forename: Takahito
authors.initials: T
authors.lastname: Nakama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kita
authors.forename: Ryo
authors.initials: R
authors.lastname: Asato
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sassa
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Arita
authors.forename: Masanori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Enaida
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oshima
authors.forename: Noboru
authors.initials: N
authors.lastname: Murakami
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Niiro
authors.forename: Junya
authors.initials: J
authors.lastname: Ono
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Goto
authors.forename: Koichi
authors.initials: K
authors.lastname: Akashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kono
authors.forename: Ali
authors.initials: A
authors.lastname: Hafezi-Moghadam
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation / Q000187:drug effects; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018630:Vitreoretinopathy, Proliferative / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015815:Cell Adhesion Molecules; C512835:POSTN protein, human
keywords: extracellular matrix; fibrosis; wound healing