Suppression of complement regulatory proteins (CRPs) exacerbates experimental autoimmune anterior uveitis (EAAU)

Purushottam Jha, Jeong Hyeon Sohn, Qin Xu, Yali Wang, Henry J. Kaplan, Puran S. Bora, Nalini S. Bora

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

This study was undertaken to explore the role of complement regulatory proteins (CRPs) in experimental autoimmune anterior uveitis (EAAU). We observed that the levels of CRPs, Crry and CD59, in the eyes of Lewis rats increased during EAAU and remained elevated when the disease resolved. The in vivo role of these CRPs in EAAU was explored using neutralizing mAbs, antisense oligodeoxynucleotides (AS-ODNs), and small interfering RNAs against rat Crry and CD59. Suppression of Crry in vivo at days 9, 14, or 19 by neutralizing mAb or AS-ODNs resulted in the early onset of disease, the exacerbation of intraocular inflammation, and delayed resolution. Suppression of CD59 was only effective when the Abs and ODNs were given before the onset of disease. The most profound effect on the disease was observed when a mixture of Crry and CD59 mAbs or AS-ODNs was administered. A similar effect was observed with a combination of Crry and CD59 small interfering RNA. There was no permanent histologic damage to ocular tissue after the inflammation cleared in these animals. Increased complement activation as determined by increased deposition of C3, C3 activation fragments, and membrane attack complex was observed in the eyes of Lewis rats when the function and/or expression of Crry and CD59 was suppressed. Thus, our results suggest that various ocular tissues up-regulate the expression of Crry and CD59 to avoid self-injury during autoimmune uveitis and that these CRPs play an active role in the resolution of EAAU by down-regulating complement activation in vivo.

Original languageEnglish (US)
Pages (from-to)7221-7231
Number of pages11
JournalJournal of Immunology
Volume176
Issue number12
DOIs
StatePublished - Jun 15 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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