geranylgeranylacetone and triethylene-glycol-dimethacrylate

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.

Topics: Animals; Blotting, Western; Choroid; Delayed-Action Preparations; Diterpenes; Drug Delivery Systems; Electroretinography; Gene Expression; Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Light; Male; Methacrylates; Polyethylene Glycols; Polymers; Polymethacrylic Acids; Rats, Sprague-Dawley; Retina; Retinal Diseases; Retinal Pigment Epithelium; Reverse Transcriptase Polymerase Chain Reaction; Sclera; Thioredoxins