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M. Ito, Y. Ueda, Y. Kobayashi, T. Wakakuri, Y. Karasawa, T. Sato, J. Imaki, M. Ishida; Regeneration of Mouse Lacrimal Gland From Ischemic Atrophy and Its Immunohistochemical Characterization. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4170.
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In our previous studies, we have shown that exorbital lacrimal gland of mice was mainly nourished by arteries from the external carotid artery, and that blocking of those vessels caused severe atrophy of the gland. We have generated an atrophy model of lacrimal gland by cauterizing those arteries in the adult mice. In the present study, we performed the longer follow-up on this atrophy model to observe the regeneration processes of mouse lacrimal gland.
After generating atrophied lacrimal gland by cauterizing the arteries nourishing exorbital lacrimal gland of 8-9 week-old C57BL/6 mice, tear volume, wet weight of the gland and histological findings of the gland by HE staining were followed up to 8 weeks. Furthermore, immunohistochemical staining for cytokeratin (CK)14, Ki67 and Caspase 3, which are markers for basal cell layer of the duct, cell proliferation and apoptosis, respectively, were performed.
In first three weeks after cauterization, tear volume and wet weight of the gland decreased by approximately 90% and 80%, respectively, while it recovered to the normal level in next 5 weeks. According to immunohistochemistry, massive atrophy occurred via apoptosis and necrosis in the first several days after cauterization. On day 3 after cauterization, epithelial proliferation began mainly in the survived ductal epithelium, followed by the expansion of the ductal system with CK14-positive epithelial cells. By 6 weeks after cauterization, apparently normal terminal acini appeared in the atrophied tissue, and by 8 weeks, those regenerated acini got predominant in the tissue.
Complete recovery from severe atrophy of the gland suggests mouse lacrimal gland have a strong regenerative potency. These results indicate that regenerative process of this ischemic model begins with the proliferation of the duct, that is similar to some other exocrine glands. Progenitor cells for lacrimal gland tissues were considered to be located in the ductal system of the gland.
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