Figure 1. Aire^GW/+ Lyn^–/– double-mutant mice develop progressive posterior uveitis.

(A) Eight- to 10-month-old Aire^GW/+ Lyn^–/– (n = 10), Aire^GW/+ (n = 4), or Lyn^–/– (n = 6) mice were analyzed by scoring of H&E-stained histological sections for presence of inflammatory infiltrates in a panel of organs consisting of eye, lacrimal gland, salivary gland, lung, pancreas, stomach, liver, and sciatic nerve. Pie graphs represent individual mice, with shaded sections indicating the presence of mononuclear infiltrate in the designated organ. The degree of shading reflects the severity of autoimmune damage, as indicated. The characteristics of all 10 double-mutant mice are shown, whereas 3 representative examples of each single-mutant mouse strain are shown. (B) Representative funduscopic images (bottom row) or H&E-stained retinal sections (top row; original magnification, ×20; scale bar: 100 μm) from 5-month-old Aire^GW/+ Lyn^–/– mice with and without uveitis and WT, Aire^GW/+, and Lyn^–/– mice. (C) Time course of histological (top row; original magnification, ×20; scale bar: 100 μm) and funduscopic (bottom row) changes in Aire^GW/+ Lyn^–/– mice with uveitis. Early changes consisted of swelling of retinal vessels and perivascular exudates (inset; original magnification, ×20; scale bar: 50 μm) leading to infiltration of mononuclear cells, development of inflammatory lesions, and destruction of the photoreceptor layer. Advanced disease was characterized by extensive retinal destruction and scarring. (n = 3 mice with uveitis analyzed longitudinally.) (D) Representative fluorescein imaging of retinal vessels in healthy (top) and diseased (bottom) 7-week-old Aire^GW/+ Lyn^–/– mice. (At least 3 mice per group were analyzed.)