A Ligation of the Lacrimal Excretory Duct in Mouse Induces Lacrimal Gland Inflammation with Proliferative Cells

Abstract

The lacrimal gland secretes tear fluids to ocular surface, which plays an indispensable role in maintaining the health of the ocular epithelia and protecting the ocular surface from the external environment. The dysfunction of the lacrimal glands causes dry eye disease due to a reduction in tear volume. The dry eye disease is becoming a popular public disease, for the number of patients is increasing, who have subjective symptom and loss of vision, which affect the quality of life. Inflammatory change in the damaged lacrimal gland has been reported; however, a major challenge is to establish a simple animal model to observe the changes. Here, we demonstrated an injury model by ligating the main excretory duct of the lacrimal gland, which is a simple and stable way to clearly understand the mechanism of lacrimal gland inflammation. We observed the process of injury and proliferation of the lacrimal gland and detected a population of lacrimal gland epithelial cells with proliferation potential which were also nestin-positive cells following duct ligation. This study successfully established an injury model to observe the tissue injury process of the lacrimal gland, and this model will be useful for analysis of the inflammation and proliferation mechanism in the future.

Regeneration of Lacrimal Gland Function to Maintain the Health of the Ocular Surface

“…The ligated artery supplies approximately 60% of blood flow to the LG in the normal state; the remaining blood supply was maintained. 24 This model exhibited a proliferative state after inflammation, which is consistent with the previous partial injury model of LGs. Similar to the rabbit model, immunohistochemical analysis showed that nestin þ cells were significantly increased in the interstitial tissues with an elongated morphology after surgery.…”

“…In the salivary gland, the ductal ligation model induced the proliferation of various cell types, including acinar, ductal, and myoepithelial cells, during tissue repair after ligature release. 23 Recently, two studies 24,25 have been reported regarding LG dysfunction in animal models (murine and rabbit) by ductal ligation. Both studies show that the ligation-injured LGs decrease in size and weight dramatically and exhibit impaired tear secretion with inflammatory cell infiltration.…”

“…Similar to the rabbit model, our study investigated main duct ligation in the mouse model for the first time. 24 Because of the small LG size and difficulty in performing the technique required to ligate the main duct of the mouse LG, no one has previously reported this model. Here, both the duct and the artery running alongside it were ligated.…”

“…After inflammation at the early stage, proliferative changes were observed involving PCNA þ cells and nestin þ cells. 24 Although the specific cell population in LGs that contributes to the regeneration is unclear, this model will be useful for investigations of such cells in LGs.…”

Advances in Functional Restoration of the Lacrimal Glands

“…temporary period of inflammation and apoptosis, tissue repair processes occur through the induction of proliferative cells expressing the stem cell markers Nestin, Ki67, ABCG2, and Sca-1. 52,54 Interstitial cells with mesenchymal cell markers, subsets of cells expressing muscle-related proteins, and epithelial mesenchymal transition pathways have also been suggested as contributing to repair processes. 55 Recent studies have revealed characteristics of the tissue stem/progenitor cells in the lacrimal glands.…”