Abstract
Purpose :
Caveolin modulators such as cavtratin are known to inhibit the activation of eNOS in vascular endothelial cells and mustard oil or carrageenan-induced tissue edema. Cavtratin reduces clinical score in the mouse experimental autoimmune encephalitis model with inhibition of CD45+ cell invasion and reduction in plasma protein extravasation across the blood brain barrier. These data suggest that caveolin modulators might be effective in uveitis.
Methods :
B10.RIII mice were immunized with human IRBP161-180 peptide in Freund’s adjuvant to induce uveitis. Mice were treated with the caveolin modulators cavtratin or CVX51401 by i.p. administration from days 7-14 post immunization. On day 14 or 15, mice were sacrificed and eyes processed for histological evaluation. Intraocular inflammation was scored by a masked evaluator according to a semi-quantitative grading scale.
Results :
Administration of caveolin modulators reduced the level of inflammation in treated eyes compared to vehicle. Histopathological grading score was reduced from 3.6 +/- 0.6 to 2.6+/-1.7 in the cavtratin group and to 2.2 +/- 1.1 in the CVX51401 group; these differences were statistically significant for CVX51401 (p=0.012); 8 animals per group.
Conclusions :
Caveolin modulators suppress inflammation in a mouse model of uveitis. This mechanism may be a promising approach to therapy in retinal inflammatory disease.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.