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.

Pharmacokinetic and Safety Evaluation of a Transscleral Sustained Unoprostone Release Device in Monkey Eyes

“…The device was intended to deliver a drug locally to the retina with less systemic circulation. [17][18][19] No significant differences in IOP between the URD-and nontreated eyes, and almost no M1 detection in plasma and anterior chamber indicated that the URD could deliver UNO locally to the retina and choroid with less systemic distribution. Unidirectional release to the scleral side by the drug-permeable cover and impermeable reservoir could contribute to the localized distribution.…”