Genetic deficiency of C3 as well as CNS-targeted expression of the complement inhibitor sCrry ameliorates experimental autoimmune uveoretinitis.
In this report, we describe the effect of complement deficiency and inhibition on experimental autoimmune uveoretinitis (EAU). C57BL/6 mice genetically deficient in C3 (C3-/-) or expressing a soluble complement activation inhibitor (soluble complement receptor related protein Y or sCrry) in a CNS-targeted fashion, (sCrry/GFAP) were induced for EAU via peripheral immunisation with a peptide of amino acids 1-20 of human interphotoreceptor retinoid binding protein in complete Freund's adjuvant with concurrent intraperitoneal pertussis toxin. The incidence and severity of EAU in the mutant mice was compared with that in simultaneously induced C57BL/6 wild type mice. The sCrry protein was detected in retinal extracts from transgenic but not wild type mice by western blot. C3-/- mice had a significant reduction in the incidence of EAU compared with wild type mice (incidence 44 versus 89%, respectively, p=0.0417) and a significant reduction in the severity of EAU (median disease score values 0 versus 1.3, respectively, p=0.0253). Similarly, sCrry mice had a significant reduction in the incidence of EAU compared with wild type mice (incidence 57 versus 100% respectively, p=0.0033) and a significant reduction in the severity of EAU (median disease score values 0.18 versus 1.85, respectively, p=0.0054). A genetic deficiency of C3 and production of a soluble complement inhibitor targeted to the CNS and eye are protective against EAU.
Read
Russell W
RW
Department of Ophthalmology, The University of Alabama at Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294-1150, USA. rwr@uab.edu
Szalai
Alexander J
AJ
Vogt
Susan D
SD
McGwin
Gerald
G
Barnum
Scott R
SR
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D015153:Blotting, Western / Q000379:methods; D002490:Central Nervous System / Q000378:metabolism; D003176:Complement C3 / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D015870:Gene Expression; D018390:Gene Targeting; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D011951:Receptors, Complement / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D017463:Receptors, Complement 3b; D012160:Retina / Q000737:chemistry / Q000378:metabolism; D012173:Retinitis / Q000276:immunology*; D014605:Uveitis / Q000276:immunology*
D003176:Complement C3; C081470:Cr1l protein, mouse; D011951:Receptors, Complement; D017463:Receptors, Complement 3b