title: Topical steroid and non-steroidal anti-inflammatory drugs inhibit inflammatory cytokine expression on the ocular surface in the botulinum toxin B-induced murine dry eye model.
abstract: OBJECTIVE
  To evaluate the effect of the topical steroid, fluorometholone, and the non-steroidal anti-inflammatory drugs (NSAIDs), nepafenac and ketorolac, on inflammatory cytokine expression of the ocular surface in the botulium toxin B-induced murine dry eye model.
  
  
  METHODS
  Topical artificial tears (0.5% carboxymethylcellulose sodium), 0.1% fluorometholone, 0.1% nepafenac, and 0.4% ketorolac were applied 3 times per day in a dry eye mouse model 1 week after intralacrimal botulium toxin B (BTX-B) or saline (sham) injection. Tear production and corneal fluorescein staining were evaluated in all groups before injection at baseline and at 3 time points up to 4 weeks after injection. The pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were evaluated by immunohistochemistry.
  
  
  RESULTS
  BTX-B-injected mice showed significantly decreased aqueous tear production and increased corneal fluorescein staining at the 1 and 2 week time points compared with normal control and saline-injected mice. In the BTX-B-injected mice, immunoﬂuorescent staining for TNF-α and IL-1β in corneal and conjunctival epithelial cells increased significantly at the 2 and 4 week time points compared to that of normal and saline-injected mice, and returned to normal levels at the 4 week time point. Topical fluorometholone significantly improved corneal surface staining in the BTX-B-injected mice after 1 week of treatment, and increased the tear production within 2 weeks, but without statistical significant difference. Topical fluorometholone significantly decreased the staining of TNF-α and IL-1β in corneal and conjunctival epithelia after 1-week treatment. Topical artificial tears, 0.1% nepafenac, and 0.4% ketorolac did not show obvious effects on tear production, corneal surface staining, and levels of IL-1β and TNF-α expression in normal, and BTX-B-injected dry eye mice.
  
  
  CONCLUSIONS
  Topical fluorometholone caused suppression of inflammatory cytokine expression on the ocular surface in the Botulium toxin B-induced murine dry eye model, while topical NSAIDs demonstrated no clearly beneficial effects.
authors: Henan Eye Institute, Zhengzhou, China
authors: Lei
authors: L
authors: Zhu
authors: Cheng
authors: C
authors: Zhang
authors: Roy S
authors: RS
authors: Chuck
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use; D044482:Benzeneacetamides / Q000008:administration & dosage / Q000627:therapeutic use; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; D003228:Conjunctiva / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003315:Cornea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D019793:Fluorescein; D005469:Fluorometholone / Q000008:administration & dosage / Q000627:therapeutic use*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020910:Ketorolac / Q000008:administration & dosage / Q000627:therapeutic use; D007765:Lacrimal Apparatus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D010648:Phenylacetates / Q000008:administration & dosage / Q000627:therapeutic use; D013666:Tears / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D044482:Benzeneacetamides; D005938:Glucocorticoids; D053583:Interleukin-1beta; D009883:Ophthalmic Solutions; D010648:Phenylacetates; D014409:Tumor Necrosis Factor-alpha; C414203:nepafenac; C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A; D005469:Fluorometholone; D019793:Fluorescein; D020910:Ketorolac