Signaling Pathways Used by the Specialized Pro-Resolving Mediator Maresin 2 Regulate Goblet Cell Function: Comparison...

Area of Science:

• Ophthalmology
• Cell Biology
• Immunology

Background:

• Specialized pro-resolving mediators (SPMs), including Maresins (MaR)-1 and 2, are crucial for maintaining tear film homeostasis and resolving ocular inflammation.
• Conjunctival goblet cells (GC) play a vital role in ocular surface health and tear film stability.

Purpose of the Study:

• To investigate the signaling pathways of Maresin 2 (MaR2) in rat conjunctival goblet cells.
• To understand the role of MaR2 and MaR1 in regulating goblet cell function and ocular surface homeostasis.

Main Methods:

• Measurement of agonist-induced intracellular calcium ([Ca2+]i) levels in goblet cells.
• Quantification of high-molecular weight glycoconjugate secretion from goblet cells.
• Exploration of G-protein coupled receptor (GPCR) and signaling pathway activation by MaR2 and MaR1.

Main Results:

• MaR2 significantly increased intracellular calcium ([Ca2+]i) and stimulated glycoconjugate secretion in goblet cells.
• Both MaR2 and MaR1 activate distinct yet overlapping GPCR and signaling pathways to modulate goblet cell function.
• MaR2 and MaR1 were found to counteract histamine-induced increases in [Ca2+]i.
• MaR2 demonstrated efficacy in resolving ocular allergy models.

Conclusions:

• MaR2 and MaR1 are key regulators of conjunctival goblet cell function, impacting tear film homeostasis.
• These SPMs utilize overlapping signaling pathways to increase intracellular calcium and stimulate secretion, contributing to ocular surface health.
• MaR2 and MaR1 represent promising therapeutic agents for inflammatory ocular surface diseases, including allergic conjunctivitis and dry eye disease, with MaR2 showing specific anti-allergy effects.