Purpose:
Gender–specific factors are known to influence some inflammatory diseases. The aim of this study was to examine the differences in severity of experimental autoimmune uveitis (EAU) between male and female wild type (WT) and complement–altered mice strains.
Methods:
Transgenic mice producing a soluble mouse complement regulator (sCrry–GFAP) or deficient for C3 (C3KO), C4 (C4KO), or factor B (FBKO ) and WT mice were induced for EAU with 0.2 ml of an emulsion containing 500 mcg IRBP in CFA supplemented with M. tuberculosis H37RA (2.5 mg per ml) SQ with concurrent pertussis toxin (1.5 mcg) IP. Eyes were collected on day 21 after immunization, placed in OCT and frozen at –80C. Serial sections (10 microns) from 6 planes across the globe were stained with H&E. EAU was graded on an 4 point scale in a masked fashion. Mann–Whitney U test was used to test for differences in severity scores.
Results:
Gender had no effect on the severity of EAU in WT mice (median severity for females 1.1 versus for males 1.1, p = 0.96). In complement system altered mice, when comparing severity of disease between males and females, no significant differences were found (C3KO females 0 versus males 0.47, p = 0.24; sCrry females 0.6 versus males 1.2, p = 0.24; FBKO females 1.1 versus males 1.8, p = 0.23; C4KO females 3.5 versus males 2.6, p = 0.52). However, when comparing WT versus complement–altered mice for each gender independently (Table), female C3KO or sCrry mice tended to develop less severe disease than did female WT mice. Males of the same strains produced lower severity scores compared to WT, but this was not significant. Female C4KO mice developed more severe disease compared to female WT mice while differences in male mice did not reach significance. No differences were found for either gender in FBKO mice.
Conclusions:
Gender had no effect on the severity of EAU in WT mice. In complement–altered mice, the data suggest that females may have more alteration in disease severity than male mice.
*All p values are a comparison between WT and each complement–altered line within gender.
Keywords: uveitis-clinical/animal model • inflammation