Dry eye disease is one of the most frequently encountered clinical problems in ophthalmology. It is common in aged individuals where atrophy and decrease in formation of tears is associated with chronic inflammation, and also occurs in Sjogren's syndrome, an autoimmune disease characterized by lymphocytic infiltration and loss of lacrimal acinar cells. Sjogren's syndrome predominantly afflicts postmenopausal women, and this implicates reproductive hormones as modulators of lacrimal gland secretory and immune function. The potential role(s) of androgens and estrogen in the etiology of lacrimal gland dysfunction is being studied extensively, but the role(s) of prolactin (PRL) is only beginning to be explored. PRL is well known as a general modulator of immune function in mammals, and the long term objective of this proposed research is to elucidate the role of PRL in the regulation of immune function in the lacrimal gland. We have obtained preliminary evidence that PRL is present in lacrimal gland acinar cells, and in this location it has both an endogenous and an exogenous origin.
The specific aims of this proposal are to: 1) Define pathways for the processing of PRL from the two origins by lacrimal acinar cells. 2) Define mechanisms involved in the regulation of release of PRL from lacrimal acinar cells. 3) Determine whether two types of receptors for PRL occur on lacrimal acinar cells, and define pathways for the processing of these receptors after binding PRL. 4) Test the hypothesis that PRL acts as an intracrine and/or autocrine regulator of the expression of Class II major histocompatibility molecules (MHC II) by lacrimal acinar cells. 5) Test the hypothesis that a PRL-like molecule secreted by lacrimal acinar cells can modulate proliferation of interstitial lymphocytes in response to antigen presentation by lacrimal acinar cells. We will use rats for in vivo studies on the uptake and secretion of exogenous PRL by the lacrimal gland, and rabbits to isolate lacrimal acinar cells for short-term culture to study the role(s) of endogenous and exogenous PRL on the regulation of surface expression of MHC II molecules by lacrimal acinar cells. Our primary approach will be light and electron microscopic immunocytochemistry to localize PRL, PRL receptors, MHC II molecules, and lysosomal enzymes. We will also use SDS-PAGE, autoradiography and RIA to identify PRL and PRL receptors, and an in vitro antigen presenting system consisting of isolated acinar cells and antigen-primed T cells to examine the role of PRL in the activation of lymphocytes by antigen presented by the acinar cells.
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