Effects of the Loss of Conjunctival Muc16 on Corneal Epithelium and Stroma in Mice

作者：Shirai Kumi^*; Okada Yuka; Cheon Dong Joo; Miyajima Masayasu; Behringer Richard R; Yamanaka Osamu; Saika Shizuya

来源：Investigative Ophthalmology & Visual Science, 2014, 55(6): 3626-3637.

DOI：10.1167/iovs.13-12955

• membrane-associated mucin
• Muc16
• cytokine
• cornea
• conjunctiva
• epithelium
• proliferation
• wound healing
• myofibroblast

PURPOSE. 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-a (TNF alpha) 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.

• 出版日期2014-6