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R.W. Read, S.D. Vogt, S.R. Barnum; Deficiency in Factor B Does Not Affect the Severity of Experimental Autoimmune Uveitis While Deficiency of C4 Exacerbates Disease Severity . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4529.
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Mice deficient in complement C3 as well as those with eye–specific production of a soluble complement inhibitor exhibit a reduced severity of EAU. The complement system is activated via one of three pathways, the alternative, classical, or mannose–binding lectin (MBL) routes. The current study’s aim was to determine which of these is primarily involved in EAU.
Previously described strains of mice deficient for C4 (C4–/–)(classical and MBL pathways) or Factor B (FB–/–)( alternative pathway) and wild–type (WT) mice were used. Mice were induced for EAU SQ with 0.2 ml of an emulsion containing 500 µg interphotoreceptor retinoid binding protein in complete Freund’s adjuvant supplemented with Mycobacterium tuberculosis strain H37RA (2.5 mg per ml) with concurrent Bordetella pertussis toxin (1.5 µg) intrapertitoneally. Eyes were collected on day 21 after immunization, placed in OCT, and frozen. Serial sections (10 microns) of each eye were stained with H&E. EAU was graded on a 4 point scale in a masked fashion. The Mann–Whitney test was used to compare median severity scores and Fisher’s exact test for differences in incidence of disease. Immunohistochemistry for IgG deposition in C4–/– and WT mice was carried out using primary antibodies against mouse IgG detected with FITC–conjugated secondary antibodies.
C4KO mice, while not exhibiting a significant difference in severity, nonetheless had marked differences in the appearance of the ocular involvement, with intense involvement of the lens. Staining for IgG deposition revealed increased staining on the lens capsule in C4KO but not WT mice.
No differences in EAU severity were seen when the alternative pathway was inhibited. Clinically worse but a statistically insignificant difference was seen in C4KO mice, with evidence suggesting that IgG deposition may play a role in the inflammation seen.
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