title: Transscleral Controlled Delivery of Geranylgeranylaceton Using a Polymeric Device Protects Rat Retina Against Light Injury.
abstract: We evaluated the effects of a transscleral drug delivery device, consisting of a reservoir and controlled-release cover, which were made of photopolymerized polyethylene glycol dimethacrylate and triethylene glycol dimethacrylate, combined at different ratios. Geranylgeranylacetone (GGA), a heat-shock protein (HSP) inducer, was loaded into the device. The GGA was released from the device under zero-order kinetics. At both 1 week and 4 weeks after device implantation on rat sclera, HSP70 gene and protein expression were up-regulated in the sclera-choroid-retinal pigment epithelium fraction of rat eyes treated with the GGA-loaded device compared with rat eyes treated with saline-loaded devices or eyes of non-treated rats. Flash electroretinograms were recorded 4 days after white light exposure (8000 lx for 18 h). Electroretinographic amplitudes of the a- and b-waves were preserved significantly in rats treated with GGA-loaded devices compared with rats treated with saline-loaded devices. Histological examination showed that the outer nuclear layer thickness was preserved in rats that had the GGA-loaded device. These results may show that transscleral GGA delivery using our device may offer an alternative method to treat retinal diseases.
authors.affiliation: Division of Clinical Cell Therapy, Center for Advanced Medical Research and Development (ART), Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, 980-8575, Sendai, Japan. nagai@med.tohoku.ac.jp.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nagai
authors.affiliation: Department of Bioengineering and Robotics, Tohoku University Graduate School of Engineering, 6-6-01 Aramaki-Aoba, Aoba-ku, 980-8579, Sendai, Japan. kaji@biomems.mech.tohoku.ac.jp.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kaji
authors.affiliation: Department of Bioengineering and Robotics, Tohoku University Graduate School of Engineering, 6-6-01 Aramaki-Aoba, Aoba-ku, 980-8579, Sendai, Japan. nishizawa@biomems.mech.tohoku.ac.jp.
authors.forename: Matsuhiko
authors.initials: M
authors.lastname: Nishizawa
authors.affiliation: Department of Ophthalmology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, 980-8574, Sendai, Japan. ntoru@oph.med.tohoku.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakazawa
authors.affiliation: Division of Clinical Cell Therapy, Center for Advanced Medical Research and Development (ART), Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, 980-8575, Sendai, Japan. toshi@oph.med.tohoku.ac.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Abe
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002829:Choroid / Q000187:drug effects / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004224:Diterpenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000295:instrumentation / Q000379:methods*; D004596:Electroretinography; D015870:Gene Expression / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008027:Light / Q000009:adverse effects; D008297:Male; D008689:Methacrylates / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D012164:Retinal Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012590:Sclera / Q000378:metabolism*; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D004224:Diterpenes; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008689:Methacrylates; D011108:Polymers; D011109:Polymethacrylic Acids; C495697:Txn1 protein, rat; C421283:poly(ethylene glycol)-dimethacrylate; C020946:triethylene glycol dimethacrylate; D011092:Polyethylene Glycols; D013879:Thioredoxins; C031049:geranylgeranylacetone
keywords: Drug delivery; Geranylgeranylacetone; Heat shock protein (HSP); Phototoxicity; Poly(ethyleneglycol) dimethacrylate (PEG); Transsclera; Tri(ethyleneglycol) dimethacrylate (TEG)