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1From the Department of Ophthalmology, and the 6Second Department of Internal Medicine, Ehime University Medical School, Ehime, Japan; the 2Department of Ophthalmology, University of Cincinnati, Cincinnati, Ohio; the 3Second Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan; the 4First Department of Anatomy, Osaka City University Medical School, Osaka, Japan; and the 5Department of Ophthalmology, Hyogo College of Medicine, Nishinomiya, Japan.
PURPOSE. To determine the association of the KL-6 epitope (sugar moiety) with MUC1 and its distribution on the ocular surface of human nondry and dry eyes.
METHODS. The human ocular surface was examined immunohistochemically and immunoelectron microscopically using monoclonal antibody (mAb) KL-6, which recognize a carbohydrate epitope of MUC1. The expression patterns of KL-6 epitope in corneal and conjunctival cells were examined by impression cytology from 24 nondry eye volunteers and 43 dry-eye patients.
RESULTS. In the cornea, bulbar conjunctiva, and limbus epithelium, mAb KL-6 reacted to the apical cell membrane of superficial cells and the intercellular space of superficial and wing cells. No immune reactivity of mAb KL-6 was observed in the basal plasma membrane of basal epithelial cells. Results of impression cytology indicated that the corneal epithelium of 13 of 24 nondry eyes was weakly stained by mAb KL-6, whereas 42 of 43 dry eyes showed a mosaic pattern. In nondry eyes, 19 of 24 bulbar conjunctival epithelia expressed the KL-6 epitope in a honeycomb pattern. In mild (17/19) and moderate (17/17) dry eye conjunctiva, the KL-6 epitope showed a mosaic pattern. However, the expression of KL-6 epitope decreased in severe dry eyes, showing a mosaic pattern in three of seven patients and labeling a few cells weakly in four of seven patients.
CONCLUSIONS. These findings suggest that there is an upregulation of the sialylated KL-6 epitope of MUC1 by apical corneal and conjunctival cells in mild and moderate dry eyes. This upregulation may in part alleviate the consequences caused by goblet cell mucin dysfunction in dry eyes. It is noteworthy that the KL-6 epitope is downregulated in the conjunctiva of severe dry eyes, a phenomenon that may be explained in part by the malfunction of conjunctival epithelial cells.
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