title: Therapeutic effect of topical adiponectin in a mouse model of desiccating stress-induced dry eye.
abstract: OBJECTIVE
  To investigate the therapeutic effect of topical adiponectin in a mouse model of experimental dry eye (EDE).
  
  
  METHODS
  EDE was created by desiccating stress in 6- to 8-week old female C57BL/6 mice. Eye drops consisting of 0.0001%, 0.001%, or 0.01% adiponectin, or balanced salt solution (BSS), were applied in EDE. Tear volume and corneal irregularity score were measured at 5 and 10 days after treatment. Levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and monokine induced by interferon-γ (MIG) were measured in the conjunctiva and lacrimal gland using a multiplex immunobead assay at 10 days. Periodic acid-Schiff staining, immunohistochemistry, and flow cytometry were also performed.
  
  
  RESULTS
  Mice treated with 0.001% or 0.01% adiponectin showed a significant improvement in tear volume and corneal irregularity compared with the EDE control and BSS-treated groups. A significant decrease in the levels of IL-1β, IL-6, TNF-α, IFN-γ, and MIG and staining intensity of TNF-α was observed in the 0.001% and 0.01% adiponectin-treated groups, compared with the other groups, in the conjunctiva and lacrimal gland. In the 0.001% and 0.01% adiponectin-treated groups, the density of conjunctival goblet cells was higher and the number of CD4+CXCR3+ T cells was lower than in the other groups. However, there were no significant differences in all parameters between the 0.0001% adiponectin and control groups.
  
  
  CONCLUSIONS
  Topical application of adiponectin can markedly improve clinical signs and decrease inflammation in the ocular surface and lacrimal gland of EDE, suggesting that adiponectin eye drops may be used as a therapeutic agent for dry eye disease.
authors.affiliation: Department of Ophthalmology and Research Institute of Medical Sciences, Chonnam National University Medical School and Hospital, Gwangju, Korea.
authors.forename: Zhengri
authors.initials: Z
authors.lastname: Li
authors.forename: Je Moon
authors.initials: JM
authors.lastname: Woo
authors.forename: Su Wol
authors.initials: SW
authors.lastname: Chung
authors.forename: Min-Young
authors.initials: MY
authors.lastname: Kwon
authors.forename: Ji-Suk
authors.initials: JS
authors.lastname: Choi
authors.forename: Han-Jin
authors.initials: HJ
authors.lastname: Oh
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Yoon
mesh_terms: D052242:Adiponectin / Q000494:pharmacology*; D000287:Administration, Topical; D000818:Animals; D003228:Conjunctiva / Q000187:drug effects / Q000378:metabolism; D003315:Cornea / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions / Q000494:pharmacology*; D054419:Receptors, Adiponectin / Q000378:metabolism; D013312:Stress, Physiological / Q000502:physiology*; D013666:Tears / Q000187:drug effects* / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D016207:Cytokines; D009883:Ophthalmic Solutions; D054419:Receptors, Adiponectin; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse