Non-muscle myosin IIC knockout enhances tear volume via disruption of ductal cell junctions in lacrimal gland

Tears are produced in the lacrimal gland through two putative water secretion pathways: transcellular pathway via water channels, and paracellular pathway via tight junctions (TJs). While the transcellular pathway is well-characterized, the existence of the paracellular pathway remains controversial. The actomyosin cytoskeleton is known to regulate TJ integrity. Here, we utilized non-muscle myosin IIC-knockout (NMIIC-KO) and NMIIC-GFP mice to investigate whether TJs regulate tear secretion. The results showed that NMIIC-GFP was enriched at the apical junction of ductal cells, but NMIIC-KO did not affect the localization of AQP5 and ZO-1. ZO-1 protein was notably reduced in NMIIC-KO lacrimal gland, while AQP5 protein level remained unchanged. NMIIC-KO mice showed increased tear volume, and moreover, brighter fluorescence in their tear when fluorescence dye was used. Our findings suggested that NMIIC-KO disrupted the tight junction of ductal cells in the lacrimal gland, implying a novel role for the paracellular pathway in tear secretion.