Abstract
Purpose :
Reduced production of the aqueous component of the tear film is a common cause of dry eye disease (DED). Prolactin (PRL), a multifunctional pituitary hormone, regularly occurs in tears. Its serum concentration has been shown to correlate with tear quality. Binding of PRL to the prolactin receptor (PRLR) induces an increased expression of prolactin inducible protein (PIP). PIP on its part leads (among other things) to an increased placement of the water channel aquaporin 5 (AQP5) into the apical cell membrane. AQP 5 occurs in human lacrimal glands (LG) and corneal epithilium (CE). Based on this, we analyzed here the influence of PRL on the expression of PIP and AQP5 in LG and CE.
Methods :
The gene expression of PRL, PRLR, and PIP in human tissue of body donators of LG and ocular surface, primary cell cultures of mice lacrimal gland epithelial cells (mLGEC) and a human corneal epithelial cell line (TEPI) is analysed by RT-PCR. Immunohistochemical analyses of formalin-fixated paraffin sections of the lacrimal apparatus verified the expression and localization of the analysed proteins at protein level. Tear fluid from DED patients and healthy volunteers was analyzed by ELISA to determine the quantity of PRL and PIP. Findings were correlated with clinical parameters of DED.
Results :
Immunohistochemistry revealed expression of PRL, PRLR, and PIP in tissue samples of the lacrimal apparatus and ocular surface for the first time. PRL and PRLR were detectable in LG, CE, meibomian glands (MG), and nasolacrimal ducts (NLD). PIP occurred in LG, CE, and MG. RT-PCR analyses demonstrated expression of PRLR in tissue samples of cornea, LG, NLD, and lid, of PIP additionally in conjunctiva. Initial analyses revealed the gene expression of PRLR and PIP in primary mLGEC as well as immortalized TEPI cells. Tear fluid from DED patients showed increased levels of PRL and PIP.
Conclusions :
PRL, PRLR, and PIP occur in the lacrimal apparatus as well as the ocular surface and are seemingly involved in physiological tear film quality. Abnormal regulation of these hormones might be associated with a reduced placement of AQP5 in lacrimal glands and epithelia of the ocular surface and might be a factor in reduced production of the aqueous component of tears. Further functional analyses are underway to demonstrate the impact of PRL-associated factors connected with DED.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.