title: Protective effects of sustained transscleral unoprostone delivery against retinal degeneration in S334ter rhodopsin mutant rats.
abstract: It has been suggested that unoprostone isopropyl (UNO) has potent neuroprotective activity in the retina. The effect of sustained transscleral UNO delivery to the posterior segment of the eye on photoreceptor degeneration was evaluated. UNO was loaded into a device made of poly(ethyleneglycol) dimethacrylate by polydimethylsiloxane mold-based UV-curing. The amount of UNO diffusing from these devices was measured using high-performance liquid chromatography. The polymeric devices that released UNO at 1.8 μg/day were implanted on the sclerae of S334ter rats at postnatal 21 days, and electroretinograms (ERGs) were compared with those of topical application and placebo devices. Retinal thickness was evaluated by histological examination. Western blots of specimens 4 weeks after implantation were performed. ERGs showed that the UNO-loaded device prevented the reduction of ERG amplitudes 2 and 4 weeks after implantation, compared with results using a placebo device or topical application. Histological examination showed that the UNO-loaded device prevented the reduction of retinal thickness, and Western blots of specimens indicated that the UNO-loaded device decreased expression of ERK1/2, phosphorylated ERK1/2, and caspase-3. A device that provided sustained UNO administration protected against retinal degeneration in rhodopsin mutant rats, and thus, may have translational potential as a sustainable method to administer drugs to treat retinitis pigmentosa. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1730-1737, 2016.
authors.affiliation: Division of Clinical Cell Therapy, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nagai
authors.affiliation: Division of Clinical Cell Therapy, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Iwata
authors.affiliation: Department of Bioengineering and Robotics, Graduate School of Engineering, Tohoku University, Sendai, 980-8579, Japan.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kaji
authors.affiliation: Division of Clinical Cell Therapy, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Sampei
authors.affiliation: Division of Clinical Cell Therapy, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Katsukura
authors.affiliation: Division of Clinical Cell Therapy, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan.|Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Onami
authors.affiliation: Department of Bioengineering and Robotics, Graduate School of Engineering, Tohoku University, Sendai, 980-8579, Japan.
authors.forename: Matsuhiko
authors.initials: M
authors.lastname: Nishizawa
authors.affiliation: Department of Ophthalmology, Tohoku University Graduate School of Medicine, Sendai, 980-8574, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakazawa
authors.affiliation: R-Tech Ueno Ltd., Chiyoda-Ku, Tokyo, 100-0011, Japan.
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Mashima
authors.affiliation: Division of Clinical Cell Therapy, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, Sendai, 980-8575, Japan. toshi@oph.med.tohoku.ac.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Abe
mesh_terms: D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation; D009154:Mutation; D051381:Rats; D011922:Rats, Mutant Strains; D012160:Retina / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D025603:Sensory Rhodopsins / Q000235:genetics* / Q000378:metabolism
chemical_list: D025603:Sensory Rhodopsins; C072630:isopropyl unoprostone; D015237:Dinoprost
keywords: poly(ethyleneglycol) dimethacrylate; retina; retinitis pigmentosa; transscleral drug delivery; unoprostone