Prolactin Inducible Protein, but Not Prolactin, Is Present in Human Tears, Is Involved in Tear Film Quality, and Influences Evaporative Dry Eye Disease

Abstract

PurposeDecreased production of the aqueous component of the tear film is an important cause of the development of dry eye disease (DED). Tear production is influenced by hormones and hormone-like factors. Prolactin (PLR), a multifunctional pituitary gland hormone, is regularly present in the lacrimal gland of rats and rabbits. In humans, serum PLR concentration correlates with tear quality. To gain deeper insights of possible effects of PRL, prolactin receptor (PRLR) and prolactin inducible protein (PIP), we analyzed the three proteins in the human lacrimal apparatus and in reflex tears of healthy volunteers as well as patients suffering from DED.MethodsGene expression of PRLR and PIP was analyzed by RT-PCR in cadaveric human lacrimal gland and ocular surface tissues, immortalized human corneal epithelial cells (HCE and hTEPI) and human Meibomian gland epithelial cells (HMGECs). At the protein level, the expression and localization of PRL, PRLR and PIP in formalin-fixed paraffin sections of the lacrimal apparatus were studied by immunohistochemistry. In addition, tear fluid from DED patients and healthy volunteers was analyzed by ELISA to determine the concentration of PRL and PIP.ResultsRT-PCR analyses revealed gene expression of PRLR and PIP in human tissue samples of cornea, lacrimal glands, and eyelids, whereas only PIP, but not PRLR, was detectable in immortalized corneal epithelial cells. Immunohistochemistry revealed for the first time the expression and localization of PRL, PRLR, and PIP in human tissues of the lacrimal apparatus and at the ocular surface. PRL and PRLR were detectable in corneal epithelium, lacrimal glands, and Meibomian glands. Reflex tears from DED patients revealed significantly increased PIP concentrations, whereas PRL was undetectable in tears of DED patients and healthy volunteers.ConclusionPRL, PRLR, and PIP are found in the lacrimal apparatus and on the ocular surface. PIP, but not PRL, is present in human tears and appears to be involved in the physiology of tear film quality. Our clinical data revealed that PIP may affect tear quality, but further functional analyses are needed to fully elucidate the effects of PRL and PIP-associated factors in tear secretion as well as in the connection of DED.

Inherited mitochondrial dysfunction triggered by OPA1 mutation impacts the sensory innervation fibre identity, functionality and regenerative potential in the cornea

“…After assessing the quantity of tears, we used sensitive untargeted mass spectrometry to analyse the tear proteome quality. Among the identified proteins, we detected factors known to be present in tears, such as lactotransferrin 26 , serum albumin 27 , prolactin inducing protein 28 , peroxiredoxin 6 and gelsolin 29 , confirming the efficiency of the proteomic analysis. Similarly to the tear production, the proteomic signature was almost not altered in the context of OPA1 mutation, regardless of the animal age (Fig.1B).…”

Prognostic Role of Prolactin-Induced Protein (PIP) in Breast Cancer

“…PIP is typically expressed in cells that possess apocrine properties, such as apocrine glands in various locations including the axilla, vulva, eyelid, ear canal, and seminal vesicle [ 13 ]. Additionally, PIP has been observed in serous cells of salivary glands, bronchial submucosal glands, and accessory lacrimal glands, which share some similarities with apocrine glands despite not being classified as typical apocrine epithelia [ 14 , 15 ]. As a secretory protein, PIP can be found in various bodily fluids such as seminal plasma, saliva, lacrimal fluid, tears, sweat gland secretion, amniotic fluid, and the blood of pregnant women [ 8 , 16 ].…”

2D-Materials-Based Wearable Biosensor Systems

“…The electrolytes in tears such as K + , Na + , Ca 2+ , Mg 2+ , and Cl − can be converted into blood electrolyte levels. For example, urea reflects the health of kidney function, glucose is present as an indicator of diabetes, various proteins are associated with diseases such as inflammation, AIDS, and cancer, and cortisol reflects the level of stress as some studies have shown a relationship between cortisol and diabetes [ 112 , 113 , 114 , 115 ].…”