September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Caveolin modulators suppress inflammation in the B10.RIII mouse model of uveitis
Author Affiliations & Notes
  • David Eveleth
    E&B Technologies, San Diego, California, United States
    CavtheRx Inc., Hamden, Connecticut, United States
  • William Sessa
    Vascular Pharmacology, Yale University, New Haven, Connecticut, United States
  • Ralph Bradshaw
    E&B Technologies, San Diego, California, United States
  • Amuthakannan Subramanian
    E&B Technologies, San Diego, California, United States
  • James T Rosenbaum
    Devers Casey Eye Institute, Portland, Oregon, United States
  • Phoebe Lin
    Devers Casey Eye Institute, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   David Eveleth, CavtheRx Inc (E), E&B Technologies LLC (E); William Sessa, CavtheRx (I); Ralph Bradshaw, E&B Technologies LLC (E); Amuthakannan Subramanian, E&B Technologies LLC (E); James Rosenbaum, E&B Technologies LLC (C); Phoebe Lin, E&B Technologies LLC (F)
  • Footnotes
    Support  NIH/NEI EY024792A
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1881. doi:
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    • Get Citation

      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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