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Wungrak Choi, ; Comparison of Inflammatory Cytokine Downregulating Effect Between TNF-α Blocker Agent and Cyclosporine A. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5653.
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Dry eye syndrome is seemed to be an inflammatory disease and we have previously shown some data about the effectiveness of topical TNF-α blocker agent for dry eye. The purpose of this study was to investigate efficacy of HL036337, a TNF-α blocker compared to cyclosporine A, for treatment of dry eye-induced inflammation and to determine the most effective dosage of HL036337 by using an experimental murine dry eye model.
HL036337 was developed by modification of the TNF receptor I. Using dry eye-induced C57BL/6 mice (N=50), corneal erosion was measured at baseline and after 4 days and 7 days of topical treatment with cyclosporine A and HL036337. To determine the effective dosage of treatment, 0.25mg/ml, 0.5mg/ml, 1mg/ml, 2.5mg/ml, 5mg/ml of HL036337 were treated topically twice a day to the dry eye induced murine cornea. Inflammatory cytokines in cornea, lymph node (LN) and lacrimal glands (LG) were measured by quantitative RT-PCR.
Dry eye induced corneal erosion was improved after 1wk topically applied cyclosporine A and 1mg/ml HL036337. Ocular surface IL-6, and LYVE-1 were significantly decreased by topical 1mg/ml HL036337. Topical 1mg/ml HL036337 also suppressed LN IL-6, IFN-γ expression.
1mg/ml HL036337, a topical TNF-α blocker effectively improved corneal erosion induced by dry eye and no significant difference was shown compared cyclosporine A. It might indicate that HL036337 is a potential agent to regulate dry eye-induced inflammation, and differences in TNF-α affinity and clearance can account for the anti-inflammatory effects on ocular regions.
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