title: Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin.
abstract: Age-related macular degeneration (AMD) is a vision-threatening disease characterized by choroidal fibrovascular membrane (FVM) formation, choroidal neovascularization (CNV) and choroidal fibrosis. No safe and effective therapeutic method has been developed for the choroidal fibrosis, although anti-vascular endothelial growth factor therapy can partially shrink the CNV. We recently reported that periostin (POSTN), which is produced by retinal pigment epithelial cells, has an important role in the formation of preretinal FVMs, but its role in choroidal FVMs has not been determined. In this study, we used Postn knockout mice to investigate the role played by POSTN in choroidal FVM formation. In addition, we used a new class of RNA interference (RNAi) agent (NK0144) that targets POSTN and determined its effect on choroidal FVM development. Genetic ablation of Postn had an inhibitory effect not only on CNV formation but also on choroidal fibrosis in a mouse CNV model. NK0144 also had a greater inhibitory effect on both the CNV and choroidal fibrosis than control RNAi with no apparent adverse effects. These findings suggest a causal relationship between POSTN and choroidal FVM formation, and also a potential therapeutic role of intravitreal NK0144 for AMD.
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakama
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Ishikawa
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Nakao
authors.affiliation: 1] Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan [2] Department of Ophthalmology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
authors.forename: Y
authors.identifier: 0000000237825351
authors.initials: Y
authors.lastname: Sassa
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Oshima
authors.affiliation: AQUA Therapeutics Co., Ltd., Kobe, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takao
authors.affiliation: AQUA Therapeutics Co., Ltd., Kobe, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Shimahara
authors.affiliation: AQUA Therapeutics Co., Ltd., Kobe, Japan.
authors.forename: K
authors.identifier: 0000000306058169
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Strategic Headquarters for Research and Development, BONAC Corporation, BIO Factory, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hamasaki
authors.affiliation: Strategic Headquarters for Research and Development, BONAC Corporation, BIO Factory, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ohgi
authors.affiliation: Strategic Headquarters for Research and Development, BONAC Corporation, BIO Factory, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Matsuda
authors.affiliation: Department of Biological Information, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kudo
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nozaki
authors.affiliation: Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ogura
authors.affiliation: Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kuroda
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ishibashi
mesh_terms: D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002829:Choroid / Q000098:blood supply / Q000473:pathology; D020256:Choroidal Neovascularization / Q000628:therapy*; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D006801:Humans; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000628:therapy*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D055213:Retinal Pigment Epithelium / Q000473:pathology / Q000502:physiology; D051196:Toll-Like Receptor 3 / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D034741:RNA, Small Interfering; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3