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David Eveleth, William Sessa, Ralph Bradshaw, Amuthakannan Subramanian, James T Rosenbaum, Phoebe Lin; Caveolin modulators suppress inflammation in the B10.RIII mouse model of uveitis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1881. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
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