Advances in experimental medicine and biology · 2016
Transscleral Controlled Delivery of Geranylgeranylaceton Using a Polymeric Device Protects Rat Retina Against Light Injury.
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Nagai Nobuhiro, Kaji Hirokazu, Nishizawa Matsuhiko, Nakazawa Toru, Abe Toshiaki
Аннотация
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.
Предметные рубрики MeSH
AnimalsBlotting, WesternChoroidDelayed-Action PreparationsDiterpenesDrug Delivery SystemsElectroretinographyGene ExpressionHSP70 Heat-Shock ProteinsHeat-Shock ProteinsLightMaleMethacrylatesPolyethylene GlycolsPolymersPolymethacrylic AcidsRats, Sprague-DawleyRetinaRetinal DiseasesRetinal Pigment EpitheliumReverse Transcriptase Polymerase Chain ReactionScleraThioredoxins