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The lacrimal gland contains stem/progenitor cells capable of tissue repair after injury. Programmed cell death after injury triggers proliferation and differentiation of these cells, presumably through activation of the BMP7 pathway.

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Several studies investigated the effect of aging on rat and human lacrimal gland physiology. However, in most of these studies, only two age groups were investigated. Furthermore, those studies did not correlate the age-related histological changes that occur in the lacrimal gland to the functional changes (nerve activity and protein secretion) that might occur with aging. Thus, the purpose of the present study was to investigate the effect of aging on lacrimal gland structure, innervation and function using BALB/c mice at different ages. Exorbital lacrimal glands were removed from 3, 8, 12, 24, and 32-month-old, male BALB/c mice, fixed, embedded and processed for histology and immunohistochemistry. Sections were stained with hematoxylin and eosin to determine morphological changes and lymphocytic infiltration; giemsa to identify mast cells; and Kinyoun's carbol fucsin solution to indicate lipofuscin-like inclusions. Parasympathetic and sympathetic nerves were identified by immunofluorescence techniques. To measure acetylcholine release and protein secretion, lacrimal gland pieces were incubated in Krebs Ringer buffer containing 5 mM KCl (control), 75 mM KCl (depolarizing buffer which activates nerves), carbachol (a cholinergic agonist, 10(-4) M), or phenylephrine (an alpha1-adrenergic agonist, 10(-4) M) for 20 min. The media were collected and analysed for acetylcholine and peroxidase using a spectrofluorometric assay. KCl-, carbachol- and phenylephrine-stimulated peroxidase secretion decreased in lacrimal glands from 8, 12, and 24-month-old mice when compared to 3-month-old animals. Both the density and distribution of parasympathetic and sympathetic nerves surrounding the acini decreased with increasing age. Acetylcholine release from lacrimal gland nerves decreased in 24-month-old mice compared to 3- and 12-month-old animals. Similarly, progressive morphological changes, including increased numbers of lipofuscin-like inclusions, mast cells and lymphocytic infiltration occurred in an age-dependent manner. We conclude that structural alterations of mouse lacrimal gland, including increased accumulation of lipofuscin-like inclusions, chronic inflammation and functional alterations including decreased acetylcholine release and protein secretion occurred with aging.

Emerging studies from our laboratory demonstrate that interleukin-1 (IL-1) family members play a major role in impairing lacrimal gland functions. Here we have extended our investigations to observe the effects of IL-1 on aqueous tear production, lacrimal gland secretion, lacrimal gland histology, and acinar and ductal cell proliferation. We demonstrate that a single injection of IL-1 into the lacrimal glands inhibited neurally- as well as agonist-induced protein secretion resulting in decreased tear output. Meanwhile, IL-1 injection induced a severe, but reversible (7-13 days), inflammatory response that led to destruction of lacrimal gland acinar epithelial cells. Finally, we demonstrate that as the inflammatory response subsided and lacrimal gland secretion and tear production returned to normal levels, there was increased proliferation of acinar and ductal epithelial cells. Our work uncovers novel effects of IL-1 on lacrimal gland functions and the potential regenerative capacity of the mouse lacrimal gland.

We studied ultrastructurally the development of rabbit corneal endothelium from the 13th day of gestation to 3 days after birth. Precursor corneal endothelial cells, stromal cells, and a vascular network migrate in close association with each other between the developing corneal and lens epithelia. During development, newly deposited extracellular fibrous matrices separate the prospective endothelium from the capillaries and corneal stroma. The extracellular matrix between the apical endothelial surface and the vascular network loses its fibrous appearance early in development. Simultaneously, randomly organized fibrils are deposited on the basal endothelial surface facing the stroma. These fibrils, gradually obscured by the deposition of a nonfibrous component, eventually become part of Descemet's membrane. Early in development, prospective endothelial cells cannot be distinguished morphologically from the overlying corneal stromal cells. Morphologic differentiation of the endothelial cell is characterized by the formation of sinuous lateral borders that interdigitate with those of adjacent cells to form a continuous single-cell layer of tissue. The basal endothelial membrane forms a pitted surface, distinguishing it from the apical cell membrane. Intercellular junctions between lateral membranes, a cilium projecting into the anterior chamber, and deposition of Descemet's membrane on the basal endothelial surface contribute to the polarization of the endothelium. Throughout most of corneal development the vascular pupillary membrane maintains a close association with the apical surface of the differentiating endothelium. We conclude that fetal corneal endothelium develops within a complex extracellular matrix environment and in proximity to the underlying vascular network. These structures play an important role in the morphogenesis of corneal endothelium.

Murine lacrimal glands contain mesenchymal stem cells that seem to play a pivotal role in tissue repair.

It was found that EMT is induced during repair of the lacrimal gland to generate MSCs to initiate repair, and that mesenchymal-epithelial transition is then activated to form acinar and ductal epithelial cells.