The Effect of TNF-α Blocker HL036337 and Its Best Concentration to Inhibit Dry Eye Inflammation

PURPOSE: Dry eye syndrome is commonly thought of as an inflammatory disease, and we have previously presented data showing the effectiveness of topical TNF-α blocker agents for the treatment of this condition. The purpose of this study was to investigate the effectiveness of the TNF-α blocking agent HL036337 compared to cyclosporine A for the treatment of dry eye induced inflammation in order to establish whether HL036337 represents a more effective method for suppressing inflammation. The efficacy of HL036337 and cyclosporine A 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/6 mice (n = 45), corneal erosion was measured at day 4 and 7 after topical treatment with cyclosporine A or HL036337. To determine the effective treatment dose, 0.25, 0.5, 1, 2.5, and 5 mg/mL of HL036337 were topically administered 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 corneal erosion was determined to be 1 mg/mL. Dry eye induced corneal erosion was improved after 1 week with topically applied cyclosporine A and HL036337 at 1 mg/mL. CONCLUSIONS: HL036337 administered topically at 1 mg/mL effectively improved corneal erosion induced by dry eye. This finding may also suggest that inhibition of TNF-α can improve dry eye syndrome.

Comparison of the Effectiveness between Sampling Methods for Protein Analysis of Tear Fluids

PURPOSE: Although various sampling methods of tears from conjunctival sac have been reported, no previous study compared their effectiveness or efficiency based on protein extraction. By comparing the compliance, volume and protein concentration of each tear sampling method, we searched for the most efficient tear collection method. METHODS: Resting tear samples of 14 eyes of normal subjects were collected using Schirmer paper, capillary tube, cellolose acetate rod and 3 different ophthalmic sponges made of different materials and density (Merocel(R), KeraCel(R) and Weck-Cel(R)). After centrifugation of the collected tear samples, the tear volume and protein concentration were measured for each method. Additionally, the compliance of each tear sampling method was analyzed by numerically representing the amount of discomfort experienced during resting tear collection. RESULTS: The average volume retrieved by each tear sampling method was 9.0 +/- 1.1 microL with no significant differences between groups. The average concentration of protein retrieved by each tear sampling method was 5.3 +/- 1.2 microg/microL. Merocel(R) retrieved 7.6 +/- 0.61 microg/microL, which was significantly higher than other sampling methods (p < 0.05). The compliance of Merocel(R) and the capillary tube were the highest, while KeraCel(R) showed the lowest compliance. CONCLUSIONS: Merocel(R) retrieved the highest amount of protein and showed high compliance and may be the most effective and easily applicable tear sampling method in clinical settings.