Early and late immunohistochemical and ultrastructural changes associated with functional impairment of the lachrymal gland following external beam radiation

Abstract

The aim of this study was to investigate scintigraphic, immunohistological and ultrastructural changes associated with radiation-induced dysfunction of the lachrymal gland in an established experimental animal model. Ten rabbits were randomized into two groups and used for the study; in the control as well as experimental group, the Schirmer-test, lachrymal gland scintigraphy, and immunohistological and ultrastructural investigations were carried out prior to irradiation and 72 h as well as 1 month after single-dose irradiation with 15 Gy. Seventy-two hours after irradiation, secretion reduction evaluated by the Schirmer-test was evident. At this phase, we could observe a decrease in the expression of alpha-SMA and a re-distribution of tenascin-C matrix. Ultrastructural changes of acinar and myoepithelial cells were noticed; simultaneously, disturbance in the primary (99m)TcO(4)- uptake as well as significant reduction of the lachrymal ejection fraction was assessed scintigraphically. These changes were still evident 1 month following irradiation but became less intensive. Single-dose irradiation with 15 Gy implicates a functional impairment of the lachrymal gland, which is associated with early immunohistological and ultrastructural alterations. These changes may represent objective surrogate parameters for radiogenic dysfunction and prerequisites for further investigations on radioprotection of lachrymal glands during radiotherapy of the periorbital region.

First-bite syndrome in oncologic patients

“…It was concluded that the early functional impairment of salivary glands after radiation could be revealed as early as 24 h after radiation. The same author, in another work [17], studied the changes of lachrymal glands in rabbits, 72 h and 1 month after 15 Gy of radiation. They found that after 15 Gy, the myoepithelial cells of the lachrymal gland presented a reduction in the -SMA of more than 50% as well as a condensation of the myoWlaments after 72 h (p < 0.05) and a reduction in the -SMA between 25 and 50% and some degree of reorganization of the myoWlaments after 1 month (p < 0.05).…”

Establishing Human Lacrimal Gland Cultures with Secretory Function

“…Over time the loss of tear film integrity induces corneal epithelial irregularities and epithelial defects [6] with higher risks of secondary infection [7] . The pathological features of dry eye include lymphocytic infiltration of the lacrimal gland [8] , reversible squamous metaplasia [8] , apoptosis of secretory epithelial cells, loss of α-smooth muscle actin and tenascin C expression in the myoepithelial cells indicating loss of function [9] . Together these contribute to reduced tear secretion and result in the signs and symptoms of dry eye.…”

Review: The Lacrimal Gland and Its Role in Dry Eye

“…Xerostomia is the most common presentation of glandular dysfunction of the head and neck; however, the lacrimal gland is also affected by radiation [ 83 ]. In rabbits, loss of smooth muscle and decreased aqueous secretion occur within 3 days of irradiation of the lacrimal gland and persist beyond thirty days [ 84 ]. Unfortunately, the long-term histopathological effects of radiation on the lacrimal gland have been poorly studied in animals and humans.…”