Intracameral toxicity of bacterial components muramyl dipeptide and staurosporine: ciliary cyst formation, epithelial cell apoptosis and necrosis

Abstract

The uveitogenic bacterial cell wall component muramyl dipeptide (MDP) is apoptogenic in rabbit kidney cells. The purpose of this investigation was to assess the cytotoxic activity of MDP and staurosporine (STSP; induces cultured corneal and lens cells apoptosis) in rabbit ciliary body tissue. Anterior uveitis was determined by clinical symptoms and increased aqueous humor (AH) protein. Ciliary body tissue was assessed for histological changes, caspase-3 activity, dye uptake, distribution of immunoreactive caspase-3 and DNA ladders at 4 and 6 hours postinjection. Increases in caspase-3 activity, APOPercentage dye uptake, and localization of immunoreactive caspase-3 in ciliary epithelial cells were associated with ciliary cysts of detached nonpigmented epithelial (NPE) cells, as well as apoptotic and necrotic DNA ladders in ciliary body tissues from eyes injected with MDP and/or STSP. The results suggest that intracameral injection of the bacterial components MDP and STSP can induce acute endophthalmic changes in uveal tissue including formation of ciliary body, NPE and pigmented epithelial (PE) cell apoptosis, and ciliary body tissue necrosis.