Pigment epithelium-derived factor (PEDF) promotes survival and contraction of myoepithelial cells in lacrimal gland

Abstract

PEDF is critical for general health of the ocular surface. In order to study mechanisms of PEDF's action in lacrimal gland (LG) secretion, these visual structures were studied in a PEDF deficient (Pedf^−/−) mouse model using biochemical, histochemical, and morphometric analyses. In Pedf^−/− animals there were several ocular surface and LG disturbances not seen in controls. Notably, changes in body and LG weight, corneal sensitivity, tear film, ocular surface damage, and size of acini comprising the LG were evident. Survival of myoepithelial cells (MECs) surrounding the acini showed a PEDF survival dependence as there were significant reduction in MEC-specific P63 cells and Bcl2 expression levels, and increased TUNEL positive cells in PEDF deficient mice. Expression levels of the major contractile MEC proteins, α-SMA, calponin, and keratin 14, were also reduced with PEDF gene deletion and MECs contraction apparatus impaired, since oxytocin significantly reduced acinar area in controls but had no effect in PEDF deficient LGs, although the oxytocin receptor (OXTR) was expressed in both PEDF genotypes. These findings suggest that PEDF is essential to MECs survival and contractile function, and tear homeostasis on the ocular surface. Treatment with PEDF is likely to alleviate ocular-related conditions in diseases associated with dry eye as well as promote healthy MEC cell function in other secretory glands of the body.