Abstract
Abstract: :
Purpose: To explore the role of the alternative pathway of complement in the development of complement-mediated uveitis. Methods: Lewis rats were divided into six groups (n=12/group). Rats in groups 1 and 2 were injected intracamerally with 5 and 50 µg zymosan suspension (5µl), respectively. Control rats (group 3) were injected with 5 µl of sterile PBS. Animals in groups 4 and 5 received purified cobra venom factor (CVF) i.p. 24 hours before receiving 5 and 50 µg zymosan, respectively. Polystyrene latex beads were used as control particles and group 6 (n=12) was injected intracamerally with 5 µl of this suspension. The development and severity of uveitis was monitored by clinical and histopathologic examination. The experiment was repeated twice. Results: Injection of zymosan (5 and 50 µg) into the anterior chamber of the eye induced severe anterior uveitis in all Lewis rats. With 5 µg of zymosan, maximum inflammation was observed between 24-48 hours and the disease resolved by day 9. However, with 50 µg of zymosan, severe inflammation persisted until day 10 with complete resolution by day 19. Histologically within 3 to 4 hours after injection of zymosan (5 or 50 µg), polymorphonuclear cells (PMNs) infiltrated the iris and ciliary body, with prominent swelling of the iris and ciliary body over the next 2 days. PMNs appeared in the anterior chamber, with spillover into the anterior vitreous; the cornea, retina and choroid was not inflamed. Pretreatment of Lewis rats with CVF completely suppressed the anterior uveitis inuced by zymosan. Intracameral injection of latex beads produced only a mild transient inflammatory reaction. Anterior uveitis did not develop in any of the animals injected with PBS. Conclusion: Our results demonstrate that the activation of the complement system via the alternative pathway can induce a severe complement-mediated anterior uveitis. The rapid onset of intraocular inflammation with a predominance of PMNs mimics certain subsets of clinical anterior uveitis which are distinct from experimental autoimmune uveits induced by uveal or retinal protein.
Keywords: 612 uveitis-clinical/animal model • 437 inflammation • 324 aqueous