The Effect of TNF-α Blocker HL036337 and Its Best Concentration to Inhibit Dry Eye Inflammation
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Purpose: Dry eye syndrome is commonly thought of as an inflammatory disease, and we have previously presenteddata showing the effectiveness of topical TNF-α blocker agents for the treatment of this condition. Thepurpose of this study was to investigate the effectiveness of the TNF-α blocking agent HL036337 comparedto cyclosporine A for the treatment of dry eye induced inflammation in order to establish whether HL036337represents a more effective method for suppressing inflammation. The efficacy of HL036337 and cyclosporineA was determined using an experimental murine dry eye model. Methods: The TNF-α blocker HL036337 is a modified form of TNF receptor I. Using dry eye induced C57BL/6mice (n = 45), corneal erosion was measured at day 4 and 7 after topical treatment with cyclosporine A orHL036337. To determine the effective treatment dose, 0.25, 0.5, 1, 2.5, and 5 mg/mL of HL036337 were topicallyadministered twice per day to dry eye induced murine corneas for 1 week. Results: The optimal concentration of the TNF-α blocker HL036337 for treatment of dry eye induced cornealerosion was determined to be 1 mg/mL. Dry eye induced corneal erosion was improved after 1 week with topicallyapplied cyclosporine A and HL036337 at 1 mg/mL. Conclusions: HL036337 administered topically at 1 mg/mL effectively improved corneal erosion induced by dryeye. This finding may also suggest that inhibition of TNF-α can improve dry eye syndrome.
Abstract
Purpose: Dry eye syndrome is commonly thought of as an inflammatory disease, and we have previously presenteddata showing the effectiveness of topical TNF-α blocker agents for the treatment of this condition. Thepurpose of this study was to investigate the effectiveness of the TNF-α blocking agent HL036337 comparedto cyclosporine A for the treatment of dry eye induced inflammation in order to establish whether HL036337represents a more effective method for suppressing inflammation. The efficacy of HL036337 and cyclosporineA was determined using an experimental murine dry eye model. Methods: The TNF-α blocker HL036337 is a modified form of TNF receptor I. Using dry eye induced C57BL/6mice (n = 45), corneal erosion was measured at day 4 and 7 after topical treatment with cyclosporine A orHL036337. To determine the effective treatment dose, 0.25, 0.5, 1, 2.5, and 5 mg/mL of HL036337 were topicallyadministered twice per day to dry eye induced murine corneas for 1 week. Results: The optimal concentration of the TNF-α blocker HL036337 for treatment of dry eye induced cornealerosion was determined to be 1 mg/mL. Dry eye induced corneal erosion was improved after 1 week with topicallyapplied cyclosporine A and HL036337 at 1 mg/mL. Conclusions: HL036337 administered topically at 1 mg/mL effectively improved corneal erosion induced by dryeye. This finding may also suggest that inhibition of TNF-α can improve dry eye syndrome.
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