Lacrimal Gland Repair after Short-term Obstruction of Excretory Duct in Rabbits

Abstract

Aqueous tear-deficient dry eye is a multifactorial chronic disorder in which the lacrimal glands fail to produce enough tears to maintain a healthy ocular surface. The existence of lacrimal gland stem/progenitor cells was proposed in several species, yet their origin and characteristics are not very clear. Here, we investigated the presence of resident progenitor cells and their regenerative potential in a rabbit model with lacrimal gland main excretory duct ligation-induced injury. The ligation-injured lacrimal glands temporarily decreased in weight and had impaired tear secretion. Protein expression profiles and transcriptional profiles were obtained from injured tissue. Isolated lacrimal gland progenitor cells were tested and characterized by stem cell-related marker evaluation, single cell clonal assay and three-dimensional (3-D) culture. The results of our study indicate that lacrimal glands are capable of tissue repair after duct ligation-induced injury, likely involving resident stem/progenitor cells and epithelial-mesenchymal transitions. Lacrimal gland progenitor cells isolated from ligated tissue can differentiate in 3-D culture. The results provide further insights into lacrimal gland stem/progenitor cell physiology and their potential for treating severe cases of tear deficiency.

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

“…Nestin þ cells are also increased in a manner similar to that of the K14 þ cells. 25 Furthermore, EMTassociated markers in LG tissues were unregulated after ductal ligation-induced injury and ligature release, in a manner similar to that of an IL-1a injection model. Cells obtained from injured LGs could proliferate from a single cell and were passaged >12 times.…”

“…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.…”

Three Dimensional Culture of Potential Epithelial Progenitor Cells in Human Lacrimal Gland

“…Besides these three epithelial cell types, the lacrimal gland stroma also contains fibroblasts that secrete extracellular matrix, and mast cells that produce histamines and matrix proteins into the interstitial spaces. The regenerative ability of lacrimal gland tissue was reported by several groups 6–8. However, researchers still debate the roles of specific cellular components in regeneration.…”

Optimization of a Rabbit Dry Eye Model Induced by Topical Instillation of Benzalkonium Chloride

“…Based on the etiology and classification of dry eye, different animal models have been developed over the years [4,5]. In rabbits, dry eye has been induced by many procedures such as dacryoadenectomy [6], female and male castration [7,8], desiccating stress [9], induced autoimmune dacryoadenitis [10], injection of the lacrimal gland with concanavalin A [11], injury of the drainage duct [12], nerve denervation [13], and topical instillation of atropine [14] or benzalkonium chloride (BAC) [15]. e current publication is focused on the topical instillation of BAC.…”