title: The Effect of TNF-α Blocker HL036337 and Its Best Concentration to Inhibit Dry Eye Inflammation.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Wungrak
authors.initials: W
authors.lastname: Choi
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyemi
authors.initials: H
authors.lastname: Noh
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Yeo
authors.affiliation: Noksibcho Hospital, Seoul, Korea.
authors.forename: Hanmil
authors.initials: H
authors.lastname: Jang
authors.affiliation: HanAll Biopharma, Seoul, Korea.
authors.forename: Hyea Kyung
authors.initials: HK
authors.lastname: Ahn
authors.affiliation: HanAll Biopharma, Seoul, Korea.
authors.forename: Yeon Jung
authors.initials: YJ
authors.lastname: Song
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Hyung Keun
authors.initials: HK
authors.lastname: Lee
mesh_terms: D000818:Animals; D003315:Cornea / Q000000981:diagnostic imaging; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015352:Dry Eye Syndromes / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D033401:Microscopy, Acoustic; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D009883:Ophthalmic Solutions; D014409:Tumor Necrosis Factor-alpha
keywords: Corneal erosion; Dry eye; HL036337; Inflammation; Tumor necrosis factor-alpha