Protective Effects of Transscleral Drug Delivery Device Against Photoreceptor Cell Death in S334ter Rhodopsin Mutant Rats

Abstract

 

Purpose

 

To evaluate the protective effects of a transscleral drug delivery device that can release unoprostone isopropyl (UNO) in a controlled release manner against photoreceptor cell death in S334ter rhodopsin mutant 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. UNO, a prostanoid for antiglaucoma eyedrops marketed in Japan, was loaded in the device. High-performance liquid chromatography was used to evaluate the release amount of UNO. After the devices were placed onto the sclera of eyes in 2 weeks old S334ter rats, flash electroretinograms were recorded. Histological examinations were perfomred to evaluate the thickness of the outer nuclear layer.

 

Results

 

UNO was released with zero-ordered kinetics from the device. Electroretinographic amplitudes of the a- and b-waves increased significantly in rats treated with UNO-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 UNO-loaded devices suppressed the retinal degeneration.

 

Conclusions

 

Transscleral UNO delivery device protected against photoreceptor cell death in S334ter rhodopsin mutant 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: 688 retina • 503 drug toxicity/drug effects