title: Different roles played by periostin splice variants in retinal neovascularization.
abstract: Retinal neovascularization (NV) due to retinal ischemia is one of the major causes of vision reduction in patients with different types of retinal diseases although anti-vascular endothelial growth factor (anti-VEGF) therapy can partially reduce the size of the retinal NV. We recently reported that periostin plays an important role in the development of NV and the formation of preretinal fibrovascular membranes, but the role of the splice variants of periostin on retinal NV has not been determined. We examined the expressions of periostin splice variants in the ischemic retinas of a mouse model of oxygen-induced retinal NV. We also studied the function of periostin splice variants on retinal NV using periostin knock out mice, and the effects of anti-periostin antibodies on retinal NV. Our results showed that the expressions of the periostin splice variants were increased in ischemic retinas. The degree of increase of periostin lacking exon 17 was the highest among the periostin splice variants examined. Both genetic ablation of periostin exons 17 and 21 and antibodies for periostin exons 17 and 21 affected preretinal pathological NV. Inhibition of exon 17 of periostin had the greatest effect in reducing preretinal pathological NV. These findings suggest a causal link between periostin splice variants and retinal NV, and an intravitreal injection of antibody for exon 17 and exon 21 of periostin should be considered to inhibit preretinal pathological NV.
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Nakama
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. Electronic address: yosida@eye.med.kyushu-u.ac.jp.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.affiliation: Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: Genetic Engineering Team, RIKEN Center for Life Science Technologies, Kobe, Japan; Animal Resource Development Unit, RIKEN Center for Life Science Technologies, Kobe, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Shioi
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Naruto
authors.initials: N
authors.lastname: Katsuragi
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.affiliation: Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, Osaka, Japan. Electronic address: taniyama@cgt.med.osaka-u.ac.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Taniyama
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005091:Exons; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012313:RNA / Q000235:genetics*; D012326:RNA Splicing; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D015861:Retinal Neovascularization / Q000235:genetics* / Q000378:metabolism / Q000628:therapy
chemical_list: D015815:Cell Adhesion Molecules; C082838:Postn protein, mouse; D012313:RNA
keywords: Extracellular matrix; Ischemia; Neovascularization; Periostin; Splice variant