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J Mo, RS Smith, MG Anderson, SW M John, JW Streilein; Participation of Innate Immune Macrophages in the Pathogenesis of Pigmentary Glaucoma in Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3393.
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Purpose: DBA/2J mice develop a genetically determined form of pigmentary glaucoma. The disease begins with peripheral transillumination as early as 4 months, evolves to include obvious pigment dispersion and elevated intraocular pressure by 6-8 months, and culminates in optic nerve atrophy beyond 10 months. We wished to determine whether innate immune cells (macrophages) appeared in aqueous humor of affected eyes and whether their appearance correlated with disease progression. Methods: Eyes of DBA/2J mice aged 2, 4, 7, and 10 months were evaluated clinically for evidence of inflammatory changes in anterior chamber and on surface of iris and lens, then removed, fixed, stained and examined by microscopy. Aqueous humor (AqH) was removed from eyes of similarly aged mice for analysis of content of protein and leukocytes. Results: AqH removed from eyes at 2 and 4 months of age was indistinguishable from normal AqH of other strains of normal mice such as BALB/c. By 6-7 months, when anterior chamber flare was detected clinically in many mice, AqH contained numerous leukocytes (∼250/µl), high levels of protein (∼7.5 mg/ml) and some samples tended to clot upon removal. At this time, pigment-containing macrophages were observed in the AqH and on the surface of lens and iris. By 10 months, few leukocytes were present in AqH, although protein levels in the fluid were higher (∼11 mg/ml). Conclusion: Onset of elevated pressure in this form of glaucoma is preceded by pigment dispersion, accumulation of pigment containing macrophages in the anterior segment, and breakdown of the blood:ocular barrier. Innate immune cells may participate in the pathogenesis of pigmentary glaucoma.
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