Atrophy and Impaired Contraction of the Myoepithelial Cells in Lacrimal Glands of Sjögren’s Syndrome Animal Models of Dry Eye Disease

Abstract

Purpose : The lacrimal gland (LG) secretory units are made up of acini and myoepithelial cells (MECs), which are able to contract to expel fluid and proteins from the acini. MECs also synthetize basement membrane and secrete growth factors. The impact of chronic inflammation on MECs function is not known; therefore, we used two well-studied animal models of human Sjögren’s syndrome, NOD and MRL/lpr mice, to investigate the effect of inflammation on MECs morphology and contraction.

Methods : MECs size was calculated on a-smooth muscle actin (SMA) stained LG sections, using ImageJ software. The amounts of myofilament proteins (SMA, calponin, and caldesmon) were determined by Western blotting. RT-PCR, Western blotting and immunohistochemical experiments were used to investigate the presence and expression of oxytocin receptors (a hormone known to induce mammary gland MECs contraction). Finally, MECs contraction in response to oxytocin stimulation was determined using confocal microscopy.

Results : Our immunohistochemical studies showed that compared to control animals; there was a statistically significant reduction in MEC size in NOD and MRL/lpr LGs. MECs from diseased LGs had significantly shorter cell processes compared to control mice and a significant reduction of general cell size. Western blotting data showed a statistically significant decrease in the amount of SMA and calponin proteins in NOD LGs when compared to control BALB/c mice. Moreover, we confirmed the presence of oxytocin receptors in the murine and human MECs. In response to oxytocin stimulation, acini areas and diameters were significantly reduced in LGs from BALB/c mice whereas those from NOD mice LGs did not. Furthermore, in unstimulated tissues, we found that acinar areas were significantly bigger in NOD versus BALB/c mice LGs.

Conclusions : We conclude that chronic inflammation of the LG first leads to atrophy of the MECs and decreased expression of myofilament proteins, which leads to impaired contraction and ultimately, impaired fluid and protein secretion from the acinar cells. MECs atrophy will also result in aberrant basement membrane secretion, leading to dysfunction of the whole LG secretory unit.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.