Abstract
Purpose :
Complement has been implicated in ocular inflammation. We have shown that ocular inflammation in murine experimental autoimmune uveitis (EAU) is mitigated by inhibiting C5 activity, either by genetic deletion or pharmacologic inhibition with an anti-C5 antibody. The present study evaluates the effect of anti-human C5 antibodies on EAU in humanized C5 mice.
Methods :
Humanized C5 mice, in which the human C5 (hC5) gene is substituted for the mouse (exon2-41), were used. EAU was induced as previously described, using pertussis toxin, IRBP and complete Frend’s. Anti-hC5 or isotype control mAb was administered through S.C injections every 3 days from day 5 to 28 post induction. OCT was used to assess levels of inflammation on days -1, 7, 14, 21 and 28. All animals were euthanized on day 28. Eyes and blood samples were harvested. Mouse anti-human(MAHA) and C5 Ab concentration were measured in the serum. Eye tissues were used for flow cytometry analysis. Data was analyzed by ANOVA.
Results :
Systemic administration of 10mg/kg of anti-hC5 significantly reduced OCT score, retina thickness and vitreous cell cluster count compared with control Ab or no treatment at week 2 and 3 (p<0.01), and no treatment at week 4 (p<0.001). Only one mouse developed a high MAHA titer in the 10mg/kg dosed group. Systemic administration of 10mg/kg of a different anti-hC5 mAb also significantly reduced OCT score, retina thickness and vitreous cell cluster count in EAU mice. This was evident by flow cytometry which demonstrated less ocular immune cell (macrophage and dendritic cells) infiltration.
Conclusions :
These results show that anti-hC5 mAbs reduce EAU disease in humanized C5 mice. C5 is a potential therapeutic target for autoimmune uveitis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.