title: Effects of the loss of conjunctival Muc16 on corneal epithelium and stroma in mice.
abstract: OBJECTIVE
  To examine the role of conjunctival Muc16 in the homeostasis of the ocular surface epithelium and stroma using Muc16-null knockout (KO) mice.
  
  
  METHODS
  We used KO mice (n = 58) and C57/BL6 (WT) mice (n = 58). Histology and immunohistochemistry were employed to analyze the phenotypes in the ocular surface epithelium. The expression of phospho-Stat3, AP-1 components, interleukin 6 (IL-6), and tumor necrosis factor-α (TNFα) in the cornea and conjunctiva was examined. The shape of the nuclei of corneal epithelial cells was examined to evaluate intraepithelial cell differentiation. Epithelial cell proliferation was studied using bromo-deoxyuridine labeling. Finally, the wound healing of a round defect (2-mm diameter) in the corneal epithelium was measured. The keratocyte phenotype and macrophage invasion in the stroma were evaluated after epithelial repair.
  
  
  RESULTS
  The loss of Muc16 activated Stat3 signal, affected JunB signal, and upregulated the expression of IL-6 in the conjunctiva. Basal-like cells were observed in the suprabasal layer of the corneal epithelium with an increase in proliferation. The loss of Muc16 accelerated the wound healing of the corneal epithelium. The incidence of myofibroblast appearance and macrophage invasion were more marked in KO stroma than in WT stroma after epithelial repair.
  
  
  CONCLUSIONS
  The loss of Muc16 in the conjunctiva affected the homeostasis of the corneal epithelium and stroma. The mechanism might include the upregulation of the inflammatory signaling cascade (i.e., Stat3 signal, and IL-6 expression in the KO conjunctiva). Current data provides insight into the research of the pathophysiology of dry eye syndrome.
authors.affiliation: Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Shirai
authors.affiliation: Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okada
authors.affiliation: Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, United States Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States.
authors.forename: Dong-Joo
authors.initials: DJ
authors.lastname: Cheon
authors.affiliation: The Laboratory Animal Center, Wakayama Medical University School of Medicine, Wakayama, Japan.
authors.forename: Masayasu
authors.initials: M
authors.lastname: Miyajima
authors.affiliation: Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, United States Department of Genetics, University of Texas MD Anderson Cancer Center, Houston, Texas, United States.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Behringer
authors.affiliation: Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamanaka
authors.affiliation: Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan.
authors.forename: Shizuya
authors.initials: S
authors.lastname: Saika
mesh_terms: D000818:Animals; D017209:Apoptosis; D018394:CA-125 Antigen / Q000096:biosynthesis / Q000235:genetics*; D003228:Conjunctiva / Q000378:metabolism* / Q000473:pathology; D003319:Corneal Stroma / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D005131:Eye Injuries / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014945:Wound Healing / Q000235:genetics
chemical_list: D018394:CA-125 Antigen; C534798:MUC16 protein, mouse; D008565:Membrane Proteins; D012313:RNA
keywords: Muc16; conjunctiva; cornea; cytokine; epithelium; membrane-associated mucin; myofibroblast; proliferation; wound healing