P2X7 receptors in the lacrimal gland: Role in health or disease?

Abstract

Presentation Description : The lacrimal gland is an exocrine gland that secretes proteins, electrolytes, and water to form the aqueous layer of the tear film. A decrease in the volume or composition of lacrimal gland fluid can contribute to dry eye disease. In addition, many of its proteins are antibacterial supporting a protective function of the ocular surface from infection. The lacrimal gland is well known for the neural regulation of its secretion with parasympathetic neurotransmitters acetylcholine and VIP, as well as the sympathetic agonist alpha1D-adrenergic agonists stimulating protein secretion. Another pathway that stimulates secretion is activation of P2X7 receptors by extracellular ATP. Activation of these receptors in lacrimal gland acini increases the intracellular [Ca²⁺] and stimulates protein secretion. In addition the three pathways muscarinic, alpha1D-adrenergic, and P2X7 interact with each other in distinct ways to alter the intracellular [Ca²⁺], but not protein secretion. Using P2X7 receptor knock out mice, activation of the P2X7 receptor appears to be beneficial as there is no increase in acinar cell pores formation and no secretion of mature IL-1b. Furthermore muscarinic agonist, alpha1D-adrenergic agonist, and ATP-stimulated increase in intracellular [Ca²⁺] was not altered in the knock out compared to control mouse lacrimal glands. Only alpha1D-adrenergic agonist stimulated protein secretion was altered and was decreased. Thus, activation of P2X7 receptors appears to play a supportive role in maintaining the health of the lacrimal gland.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.