Abstract
Purpose:
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.
Methods:
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.
Results:
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.
Conclusions:
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.