Differential Effect of Macrophage Depletion on Two Forms of Experimental Uveitis Evoked by Pigment Epithelial Membrane Protein (EAPU), and by Melanin-Protein (EMIU)

Abstract

The purpose of the present study was to clinically and histologically investigate the influence of macrophage depletion on the development of experimental autoimmune pigment epithelial membrane protein-induced uveitis (EAPU), and experimental melanin-protein induced uveitis (EMIU) in the Lewis rat. EAPU is mainly characterized by pigment epitheliitis. Posterior mononuclear cell accumulations enclose and destroy the retinal pigment epithelium (RPE). In EMIU the inflammation is specifically localized in the uvea.EAPU was induced by immunization with RPE membrane protein, and EMIU was evoked by immunization with purified choroidal melanin. Systemic treatment with dichloromethylene diphosphonate (Cl2MDP)-containing liposomes just before the expected beginning of the clinical signs of EAPU (at day 7 and 9 after immunization) resulted in a considerable delay of the uveitis process. In the treated animals the typical plaque shaped cell accumulations (containing many macrophages) along the RPE were lacking. Two weeks after the treatment, severe rebound EAPU developed. Local treatment by subconjunctival liposome injections did not exert any effect on EAPU. In EMIU, macrophage depletion by systemic treatment did not noticeably influence the clinical and histological development of the inflammation.Systemic treatment at the peak stage of EAPU (at day 12 and 14 after immunization) resulted in the rapid disappearance of the clinical signs of uveitis. Vitreous and anterior chamber cells were virtually absent two days later. This situation remained unchanged until the experiment was terminated two weeks later. Already deposited cell accumulations along the RPE did not regress but stopped their progression.Hematogenous macrophages thus appear to play a crucial role in the development of EAPU but the effect of early macrophage depletion on EAPU appeared to be temporary due to blood repopulation. A possible explanation for the differential influence of macrophage depletion on EAPU and EMIU is discussed, and is based on differences in immunopathogenesis.