Topical Administration of Unoprostone Provides Retinal Protection Against Retinal Degeneration of Rhodopsin P23h Rats by Inhibiting Apoptosis

Abstract

Purpose: : Isopropyl unoprostone (unoprostone) is an antiglaucoma agent which also has a neuroprotective activity by calcium blocking effects and increase of retinal blood flow. We investigated to determine whether unoprostone delays retinal degeneration induced by rhodopsin P23H transgenic (P23H) and Royal College of Surgeons (RCS) rats or not.

Methods: : Unoprostone was topically administrated to P23H and RCS rat eyes twice a day for 2 weeks. Thereafter, retinal morphology and function were examined by light microscopy and electroretinogram, respectively. Gene expression profiles were analyzed by a microarray system (Illumina) by using P23H rat retina with or without administration of unoprostone.

Results: : The P23H rats demonstrated significant preservation of both the thickness of outer nuclear layer and the amplitude of b-wave in ERG after unoprostone administration. However, the RCS rats did not show any significant differences in retinal morphology and ERG amplitude between unoprostone treated and control eyes. Microarray analysis showed up-regulation of bcl-2 and down-regulation of caspases 6 and 12 after unoprostone administration in P23H rats.

Conclusions: : Topical administration of unoprostone delays retinal degeneration caused by P23H rat by inhibiting apoptosis, although the exact mechanisms are currently unknown.

Keywords: neuroprotection • drug toxicity/drug effects • transgenics/knock-outs