title: Effect of 0.025% FK-506 eyedrops on botulinum toxin B-induced mouse dry eye.
abstract: OBJECTIVE
  To investigate the effect of FK-506 eye drops on Botulinum toxin B (BTX-B)-induced mouse dry eye.
  
  
  METHODS
  Forty-five CBA/J mice were followed up for 4 weeks after treatment with 0.025% FK-506, vehicle or 0.9% saline eye drops 3 days after intralacrimal glands injection with 20 milliunits BTX-B. Tear production, corneal fluorescein staining, the mRNA, and protein expression of cytokines were measured. The activation of nuclear factor-κB (NF-κB) was detected by Western blotting. The infiltration of inflammatory cells was examined by immunohistochemistry.
  
  
  RESULTS
  After treated with FK-506 eye drops, aqueous tear production in the mice began to recover at week 1, and then increased to the levels of pre-BTX-B injection at week 4 (2.21 ± 0.43 vs. 2.52 ± 0.71 mm, t = 0.84, P > 0.05). The severity of corneal epithelial defects was alleviated at week 2 and further improved at week 4 when compared with those in the vehicle- and saline-treated groups. The gene expression of IL-1β and TNF-α in the FK-506 and vehicle-treated groups were 47.01% and 45.56%, 85.91% and 115.83% of that in the saline-treated group in the ocular surface, while in the lacrimal glands 49.16% and 67.60%, 94.91% and 95.77% of that in the saline-treated group, respectively. The ratio of phosphorylated IκB-α to total IκB-α in the keratoconjunctival tissues was lower in the FK-506-treated group than in the vehicle- and saline-treated groups (both P < 0.05). No inflammatory cells were detected in all groups.
  
  
  CONCLUSIONS
  Topical application of FK-506 can inhibit NF-κB activation and related inflammatory response and alleviate the signs of dry eye.
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center of Sun Yat-sen University, Guangzhou, China.
authors.forename: Bin-wu
authors.initials: BW
authors.lastname: Lin
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center of Sun Yat-sen University, Guangzhou, China Department of Ophthalmology, Fuzhou Dongfang Hospital, Xiamen University, Fuzhou City, Fujian Province, China.
authors.forename: Mei-zhu
authors.initials: MZ
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center of Sun Yat-sen University, Guangzhou, China.
authors.forename: Shu-xian
authors.initials: SX
authors.lastname: Fan
authors.affiliation: The Department of Ophthalmology and Visual Science, Montefiore Medical Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York, United States.
authors.forename: Roy S
authors.initials: RS
authors.lastname: Chuck
authors.affiliation: The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center of Sun Yat-sen University, Guangzhou, China.
authors.forename: Shi-you
authors.initials: SY
authors.lastname: Zhou
mesh_terms: D000818:Animals; D019274:Botulinum Toxins, Type A / Q000633:toxicity; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015352:Dry Eye Syndromes / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D007765:Lacrimal Apparatus / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D009883:Ophthalmic Solutions; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D009883:Ophthalmic Solutions; C096323:rimabotulinumtoxinB; D019274:Botulinum Toxins, Type A; D016559:Tacrolimus
keywords: FK-506; NF-κB; dry eye; inflammation