The effect of endothelin receptors in experimental rabbit uveitis model

Uveitis is a disease that affects uvea and besides it can damage vitreus, retina and optic nerve. The pathogenesis of uveitis is not fully understood and there are several ongoing studies about treatment modalities. Endothelin is considered the most potent vasoconstrictor peptide. Since its discover, endothelin has been under focus of several medical sciences. Endothelin receptors have been shown in the eye and it was reported that they induced the increase at aqueous protein concentration. There are limited studies investigating the effects of endothelin receptors at ocular tissues. The aim of this study is to evaluate clinical activity score, anterior chamber inflammatory cell counts, aqueous protein concentration and histopathologic changes in Bosentan (non-selective endothelin receptor antagonist) and BQ123 (ETA receptor antagonist) injected groups. For this purpose 42 eyes of 42 rabbits were used. The animals were divided into 7 groups and there were 6 rabbits at each group (V: saline and ethanol, B: Bosentan, BQ: BQ123, LPS: Lipopolysaccharide, BL: Bosentan and Lipopolysaccharide, BQL: BQ123 and Lipopolysaccharide, K: saline injected groups). The drugs were applied via subtenon route one hour before LPS injection. At statistical analysis, BQ123 decreased clinical score, cell counts and protein amount more than Bosentan and it was significant for cell counts (p=0.018). Bosentan diminished inflammatory reactions more than BQ123 at histopathological specimens. This decrease was statistically significant (p=0.002). As a result, ETA receptor blockage is effective on uveitis treatment by its protective effect on blood aqueous barrier and non-selective endothelin receptor blockage antagonizes the vascular step of uveitis. Keywords: Endothelin, endothelin receptor antagonists, uveitis, lipopolysaccharide, endotoxin.