title: Transscleral sustained vasohibin-1 delivery by a novel device suppressed experimentally-induced choroidal neovascularization.
abstract: We established a sustained vasohibin-1 (a 42-kDa protein), delivery device by a novel method using photopolymerization of a mixture of polyethylene glycol dimethacrylate, triethylene glycol dimethacrylate, and collagen microparticles. We evaluated its effects in a model of rat laser-induced choroidal neovascularization (CNV) using a transscleral approach. We used variable concentrations of vasohibin-1 in the devices, and used an enzyme-linked immunosorbent assay and Western blotting to measure the released vasohibin-1 (0.31 nM/day when using the 10 μM vasohibin-1 delivery device [10VDD]). The released vasohibin-1 showed suppression activity comparable to native effects when evaluated using endothelial tube formation. We also used pelletized vasohibin-1 and fluorescein isothiocyanate-labeled 40 kDa dextran as controls. Strong fluorescein staining was observed on the sclera when the device was used for drug delivery, whereas pellet use produced strong staining in the conjunctiva and surrounding tissue, but not on the sclera. Vasohibin-1 was found in the sclera, choroid, retinal pigment epithelium (RPE), and neural retina after device implantation. Stronger immunoreactivity at the RPE and ganglion cell layers was observed than in other retinal regions. Significantly lower fluorescein angiography (FA) scores and smaller CNV areas in the flat mounts of RPE-choroid-sclera were observed for the 10VDD, VDD (1 μM vasohibin-1 delivery device), and vasohibin-1 intravitreal direct injection (0.24 μM) groups when compared to the pellet, non-vasohibin-1 delivery device, and intravitreal vehicle injection groups. Choroidal neovascularization can be treated with transscleral sustained protein delivery using our novel device. We offer a safer sustained protein release for treatment of retinal disease using the transscleral approach.
authors.affiliation: Division of Clinical Cell Therapy, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Onami
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nagai
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kaji
authors.forename: Matsuhiko
authors.initials: M
authors.lastname: Nishizawa
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Sato
authors.forename: Noriko
authors.initials: N
authors.lastname: Osumi
authors.forename: Toru
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Abe
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000008:administration & dosage*; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism; D003094:Collagen / Q000737:chemistry; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D004867:Equipment Design; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008027:Light; D011092:Polyethylene Glycols / Q000378:metabolism; D051381:Rats; D012164:Retinal Diseases / Q000628:therapy; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D012590:Sclera / Q000187:drug effects*
chemical_list: D018797:Cell Cycle Proteins; C552060:VASH1 protein, rat; D011092:Polyethylene Glycols; D003094:Collagen