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ME Stern, J Gao, C Vu, K Qadeer, S Morales, LA Wheeler; Topical Steroid Induced Inflammatory Cell Death In Lewis Rats With Endotoxin-induced Uveitis (eiu) . Invest. Ophthalmol. Vis. Sci. 2002;43(13):45.
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Purpose: Endotoxin-induced uveitis (EIU) is an acute intraocular inflammation characterized by a rapid inflammatory cell infiltration and protein accumulation in the aqueous humor. Various agents including systemic steroids such as prednisolone acetate (10 mg/kg bw) have been studied in EIU for their anti-inflammatory capacities. In the current study, Pred Forte® (1%) ophthalmic suspension (Allergan, Inc.) was evaluated for the effectiveness of topical prednisolone in inhibiting ocular inflammation. Additionally, the role of Pred Forte in the induction of inflammatory cell death was also investigated as part of its anti-inflammatory mechanism. Methods: EIU was induced in female Lewis rats by a single foot-pad injection using 100 ug LPS. The first dose of Pred Forte® (1%) (equivalent to 5 mg/kg bw) was given topically prior to LPS administration. Two additional doses were given post LPS injection with 4 hour interval. Saline was used for the control animals. At 16 and 24 hours following LPS treatment, the aqueous humor from the right eye was collected for quantifying inflammatory cell counts and protein concentrations. The globe from the left eye was prepared for histological analysis. The viability of inflammatory cells in the aqueous humor was assessed using differential uptake of fluorescence DNA binding dyes acridine orange and ethidium bromide. Results: Topical Pred Forte® (1%) significantly inhibited anterior uveitis at 24 hours post LPS administration as measured by the decrease in the number of inflammatory cells and protein concentration in the aqueous humor. Sixteen hours post LPS injection, the majority of inflammatory cells were found to be non-viable via either apoptotic or necrotic cell death in the Pred Forte-treated rats. In control rats however, most cells were still viable even at 24 hours after LPS injection. Conclusion: These results demonstrate that topical prednisolone is efficacious in treating acute ocular inflammation in Lewis rats with EIU. The effect of prednisolone in blocking inflammatory cell accumulation in the anterior chamber may be due to its facilitation in the inflammatory cell death.
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