Abstract
Purpose :
Decreased production of the aqueous tear film component 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, its prolactin receptor (PRLR) and prolactin inducible protein (PIP) occur in the human ocular surface and lacrimal apparatus. So far, it is not yet understood which impact these hormones have on the development of DED. To gain deeper insights in their possible effects, we analyzed the three proteins in human cell lines of ocular surface tissues and in reflex tears of healthy volunteers as well as patients suffering from DED.
Methods :
Gene expression of PRLR and PIP was analyzed by reverse transcription polymerase chain reaction (RT-PCR) in immortalized human cell lines of differentiated and undifferentiated meibomian glands (hMGEC; n=2), human cornea epithelium (HCE; n=2 and hTCEpi; n=2), human conjunctiva epithelium (HCjE; n=2) and human lacrimal gland epithelium (hLGEC; n=3). In addition, tear fluid from DED patients (n=115) and healthy volunteers (n=38) was analyzed by ELISA to determine the concentration of PRL and PIP.
Results :
RT-PCR analyses revealed gene expression of PRLR and PIP only in hLGEC. Differentiated and undifferentiated hMGEC and hTCEpi expressed PIP, but not PRLR. HCE and HCjE expressed neither PIP nor PRLR. Reflex tears from DED patients revealed significantly increased PIP concentrations, whereas PRL was undetectable in tears of DED patients and healthy volunteers. Especially patients with a mixed aqueaous deficient and hyperevaporative DED showed significantly increased PIP with 934.8 ± 301.5 pg/mg compared to 157,7 ± 13,5 pg/mg PIP in healthy tears (p < 0.01). In total, the PIP concentration was higher in females and in subjects over 50 years.
Conclusions :
Even though PRL, PRLR, and PIP occur in human tissue of meibomian glands, cornea, conjunctiva, and lacrimal glands, their human cell lines do not show the same characteristics. Only the human cell line of the lacrimal gland does and can therefore be used for further investigations regarding the role of PRL and PIP at the ocular surface. PIP seems to affect tear quality and correlates with sex and age. Further functional analyses, especially stimulation tests with the hLGEC, are underway to demonstrate the impact of PRL-associated factors connected with DED.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.