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M.P. Langford, R. Chanis, J. Gosslee, J.P. Ganley, R.P. Misra, D.E. Texada; Ciliary Cysts Formation and Epithelial Cell Apoptosis in Aged Rabbits Induced by Intracameral Muramyl Dipeptide and Staurosporine . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1913.
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Muramyl dipeptide (MDP) is a potent adjuvant, but can exert dose–dependent apoptogenic and necrotic effects in vitro and in experimental animal models of inflammation. The purpose of this investigation was to assess the acute pathological changes induced by apoptogenic bacterial components MDP and staurosporine (STSP) in aged rabbits.
Caspase–3 activity was assessed to quantify apoptosis in iris/ciliary body tissue at 4 and 6 h. The pathology within ciliary body tissue of eyes of 3–5 year–old rabbits injected with placebo, MDP and STSP was assessed at 6 h post intracameral injection. Caspase–3 positive ciliary epithelial cells were detected by immunofluorescent antibody. In addition, DNA ladder analysis were performed to detect and in ciliary body tissue.
Ciliary cysts caused by apical detachment of the nonpigmented epithelial (NPE) cell layer were detected 6 h post MDP and STSP injection. Caspase–3 activity levels were 2–fold higher (p=0.03) at 4 h post injection in ciliary body tissue from MDP–injected eyes (10 ±1.4 U/mg wet weight) than from placebo–injected eyes (5.4±1.4 U/mg wet weight) and 5–fold higher (p=0.003) in ciliary body tissue from MDP–injected (67±18 U/mg) than in placebo–injected eyes (13±11 U/mg wet weight) at 6 h post injection. Further, caspase–3 activity in ciliary body tissue from the STSP–injected eyes (48±25 U/mg wet weight) was higher (p=0.03) than in ciliary body tissue from un–injected control eyes (5.2±4.6 U/mg wet weight). Caspase–3 positive PE and NPE cells and DNA ladders were detected in ciliary body tissue.
We demonstrate MDP and STSP induced ciliary apoptosis in vivo and formation of ciliary cysts in association with caspase–3 mediated ciliary epithelial cell apoptosis in aged rabbit eyes.
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