Abstract
Abstract: :
Purpose: The expression of complement regulatory proteins has previously been demonstrated in the normal corneal epithelium and stroma. The purpose of this study was to explore the role of these proteins and the complement system in corneal inflammation.Methods: The role of the complement system in the cornea was analyzed by using neutralizing monoclonal antibodies against the complement regulatory proteins in normal Lewis rats and BALB/c mice. Animals were injected subconjunctivally with 25 µg of anti–CD59, anti–Crry, or a combination of both antibodies. The injections were performed either once or twice in a 24 hour interval. Controls were injected with an equal amount of normal mouse IgG. Corneas were followed for 7 days and the onset, duration and severity of corneal inflammation monitored by slit–lamp examination and histological analysis in a masked fashion. Results: Injection of antibodies against complement regulatory proteins resulted in the development of spontaneous keratitis after 24 hours both in the rat and murine model. The inflammation peaked at 36 hours and resolved 48 hours after the last injection. In eyes treated with the combination of anti–Crry and anti–CD59, a more severe inflammation was observed compared to eyes treated with only one of these antibodies. While eyes that were injected once expressed a mild inflammation, close to the injection site, eyes that received a second injection at 24 hours, demonstrated a more severe form of keratitis throughout the cornea. Control eyes, however, did not show any signs of inflammation. Histological analysis of corneas revealed a heavy infiltration of polymorphonuclear cells and to a lesser degree, mononuclear cells. Conclusions: We provide, for the first time, in vivo evidence that corneal inflammation can be induced by inhibition of complement regulatory proteins both in rats and mice. Furthermore, these results suggest that low level chronic activation of the complement system (i.e. the innate immune system) may exist similar to the anterior chamber of the eye, presumably to protect the cornea from infectious pathogens.
Keywords: immunomodulation/immunoregulation • cornea: basic science • keratitis