LIPOSOME-ENCAPSULATED CLODRONATE RETARDS THE DEVELOPMENT OF EXPERIMENTAL AUTOIMMUNE UVEITIS

A study was undertaken to determine if the intravenous injection of li posome-encapsulated dichloromethylene diphosphonate (Cl2MDP; Clodronat e(TM)), a treatment known to deplete monocytes, as well as liver and s pleen macrophages, would reduce the number of macrophages in the retin a of animals with experimental autoimmune uveitis (EAU) and decrease t he severity of the disease. EAU was induced in Lewis rats by immunizat ion with S-antigen (S-Ag). Monocytes and macrophages were depleted via an intravenous injection of Cl2MDP encapsulated in liposomes. Control groups included rats that received no S-Ag (n=18), S-Ag and no treatm ent (n=23), S-Ag and free drug (n=20), or empty liposomes (n=14). Trea ted animals received injections of the Cl2MDP-liposomes, free drug, or empty liposomes. Animals were sacrificed at 14, 21 and 28 days post-S -Ag administration. Intravenous, Cl2MDP-liposomes produced a statistic ally significant reduction in the severity of the EAU when compared to controls at both days 14 and 21 following S-Ag injection. Immunohisto chemical staining with the monoclonal antibody ED1 demonstrated that t he severity of the ocular inflammatory response correlated with the nu mber of ED1-positive cells in the retina. Following the cessation of t reatment, treated animals developed disease that was as severe at day 28 as that of untreated animals at day 21. These results confirm the i mportance of monocytes and macrophages in EAU by demonstrating the cor relation between the presence of ED I-positive cells in the retina and the resultant damage to the retina. Although the dosing regimen emplo yed here did not provide a cure, strategies designed to prevent the lo cal recruitment and/or activation of mononuclear phagocytes may prove to be useful in the treatment of EAU.