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Leslie Wilson, Russell Van Gelder, Kathryn Pepple; Systemic antigen exposure increases intraocular inflammation in primed mycobacterial uveitis (PMU). Invest. Ophthalmol. Vis. Sci. 2018;59(9):2546. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Uveitis can result in severe visual impairment, and ranks fifth among causes of blindness in the United States. Animal model studies, primarily in experimental autoimmue uveitis (EAU), have provided the current understanding of disease pathogenesis. Due to the heterogeneity of disease manifestations in humans, multiple well characterized animal models with non-overlapping features are required to best represent the human disease spectrum. Primed mycobacterial uveitis (PMU) is an acute, spontaneously resolving, anterior and intermediate uveitis previously studied in rabbits and rats. We report here the adaptation of this model for use in mice, and test the impact of subcutaneous priming on ocular inflammation.
Uveitis was induced in C57Bl6/J mice with (PMU) or without (UPMU) subcutaneous injection of 0.1 mg killed mycobacterium tuberculosis H37Ra extract in mineral oil followed by intravitreal injection of 5μg H37Ra extract in PBS seven days later. Clinical inflammation was scored by daily optical coherence tomography (OCT) imaging for one week followed by weekly imaging for one month. Whole eyes were collected for histology, or aqueous was collected on Day1, Day2 (peak inflammation) or Day28 (remission). Total protein was quantified by colorometric assay. Sham injection was performed as a control.
PMU generates an acute anterior and intermediate uveitis without retinal involvement. Clinical scores and aqueous protein were significantly higher in PMU when compared to unprimed PMU or Sham controls on the days of peak inflammation. There was no significant difference between unprimed PMU and Sham. By day 28, clinical score and aqueous protein decreased significantly from peak levels in PMU, but did not return to baseline.
Primed Mycobacterial Uveitis (PMU) generates a robust model of anterior and intermediate uveitis in mice that significantly resolves within one month. The time course of inflammation, and absence of retinal involvement makes this a good compliment to EAU for modeling the spectrum of human disease. Availability of genetic mutants and antibodies in mice make this model a good target for future studies into the mechanisms of uveitis inflammation.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
AC inflammation peaks at day1-2, then resolves. Vitreous inflammation peaks later, day 5-7, and resolves later.
Aqueous protein was significantly higher in PMU than UPMU and Sham at peak inflammation.
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