Protective Effects of Transscleral Drug Delivery Device Against Light-induced Retinal Damage in Rats

Abstract

 

Purpose:

 

To evaluate the protective effects of a transscleral drug delivery device that can release geranylgeranylacetone (GGA) in a controlled release manner against light-induced retinal damage in rats.

 

Methods:

 

The device consists of a reservoir, controlled-release cover, and drug formulations, which were made of photopolymeized poly(ethyleneglycol) dimethacrylate that partially contains tri(ethyleneglycol) dimethacrylate. These parts were fabricated via a microfabrication technique that used an AutoCAD design. GGA, a heat shock protein (HSP) inducer, was loaded in the device. High-performance liquid chromatography was used to evaluate the release amount of GGA. After the devices were placed onto the sclera of rat eyes, HSP inductions of retinal tissues were evaluated by real-time RT-PCR and western blot analyses. Flash electroretinograms were recorded 4 days after white light exposure (8000 lux for 18h). Histological examinations were perfomred to evaluate the thickness of the outer nuclear layer.

 

Results:

 

GGA was released with zero-ordered kinetics from the device. One or four weeks after implanation, gene and protein expression of HSP70 were upregulated in the sclera-choroid-retinal pigment epithelium fraction of the eyes treated with GGA-loaded devices compared with those treated with saline-loaded devices or non-treated rats. Electroretinographic amplitudes of the a- and b-waves increased significantly in rats treated with GGA-loaded devices compared with saline-loaded devices. The outer nuclear layer thickness was thinned in the group treated with saline-loaded devices, but the group treated with GGA-loaded devices suppressed the photic damage.

 

Conclusions:

 

Transscleral GGA delivery device protected against light-induced retinal damage in rats. The device may offer a less-invasive method of drug delivery to achieve sustained release of medications for intravitreal drug delivery and the treatment of various retinal diseases.

 

Keywords: age-related macular degeneration • drug toxicity/drug effects • retina