Abstract
The purpose of the present studies was to investigate the impact of chronic inflammation of the lacrimal gland, as occurs in Sjögren’s syndrome, on the morphology and function of myoepithelial cells (MECs). In spite of the importance of MECs for lacrimal gland function, the effect of inflammation on MECs has not been well defined. We studied changes in MEC structure and function in two animal models of aqueous deficient dry eye, NOD and MRL/lpr mice. We found a statistically significant reduction in the size of MECs in diseased compared to control lacrimal glands. We also found that oxytocin receptor was highly expressed in MECs of mouse and human lacrimal glands and that its expression was strongly reduced in diseased glands. Furthermore, we found a significant decrease in the amount of two MEC contractile proteins, α-smooth muscle actin (SMA) and calponin. Finally, oxytocin-mediated contraction was impaired in lacrimal gland acini from diseased glands. We conclude that chronic inflammation of the lacrimal gland leads to a substantial thinning of MECs, down-regulation of contractile proteins and oxytocin receptor expression, and therefore impaired acini contraction. This is the first study highlighting the role of oxytocin mediated MEC contraction on lacrimal gland function.
Highlights
The non-keratinized epithelia of the ocular surface are constantly challenged by environmental insults such as smoke, dust, or airborne pathogens
To address the impact of inflammation on myoepithelial cells (MECs) morphology, we developed a method to estimate the size of α-smooth muscle actin (SMA) stained lacrimal gland MECs (Fig. 1B)
Lacrimal gland sections from diseased and control animals were stained with an antibody against SMA and MEC size was measured as described in the Methods section
Summary
The non-keratinized epithelia of the ocular surface are constantly challenged by environmental insults such as smoke, dust, or airborne pathogens. Production of tears in insufficient quantity or of inadequate quality results in constant irritation of the ocular surface leading to dry eye disease referred to as keratoconjunctivitis sicca (KCS)[5]. Dry eye disease secondary to lacrimal gland deficiency is referred to as aqueous-deficient type of dry eye and can occur as a result of autoimmunity, such as Sjögren’s syndrome[5]. MECs synthesize components of the basement membrane and secrete growth factors and are thought to be able to contract to expel fluid and proteins from the acini[24,25,26]. MECs are best studied in the mammary gland where it was shown that their contraction is crucial for milk production and that knockout of SMA expression leads to impaired milk secretion[27]. Despite their potential critical role in lacrimal gland secretion, very little is known about MEC contraction in this tissue, nor the impact of chronic inflammation of the lacrimal gland on these cells
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
