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Wendy Kam, David A. Sullivan; Vasoactive Intestinal Peptide Stimulates the Adenylyl Cyclase Pathway in Immortalized Human Meibomian Gland Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3730.
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A remarkable characteristic of the human meibomian gland is its rich sensory, sympathetic and parasympathetic innervation. No other human sebaceous gland shares this characteristic, yet the functional relevance of these nerve fibers is unknown. We hypothesize that neurotransmitters are secreted in the vicinity of the gland; act upon glandular receptors; and modulate the production, secretion, and/or delivery of meibum to the lid margin. If our hypothesis is correct, then the nervous system plays an important role in maintaining the tear film lipid layer, and thus the health of the ocular surface. Our objective in this study was to begin to determine whether neurotransmitters do influence the meibomian gland. Towards that end we evaluated whether [a] the activity of the adenylyl cyclase pathway, which mediates several neurotransmitter activities and generates cAMP, is measurable in meibomian gland epithelial cells; and [b] vasoactive intestinal peptide (VIP), which is present in nerves adjacent to the gland, stimulates this pathway.
Immortalized human meibomian gland epithelial cells were exposed to VIP and/or forskolin, in the presence or absence of phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Intracellular cAMP levels were quantitated with a colorimetric enzyme-linked immunoassay.
Our findings demonstrate that forskolin, a secretagogue known to activate adenylyl cylase, increases cAMP levels in human meibomian gland epithelial cells. This forskolin action is amplified in the presence of IBMX. Similarly, our results show that VIP, in combination with forskolin or IBMX, but not alone, dramatically increases intracellular cAMP content.
Our research demonstrates that VIP does influence the function of human meibomian gland epithelial cells. It remains to be determined whether this effect modulates the production, secretion and/or delivery of meibum to the ocular surface.
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