The data presented in this manuscript along with studies

The data presented in this manuscript along with studies by Lippested et al. using RvD1 (Lippestad et al., 2017) and Hodges et al. (2017) using LXA4, support the hypothesis that these SPMs play a dual role in the conjunctival goblet cells. The first role is to maintain homeostasis in normal, non-inflamed conjunctiva. In support of this, we demonstrated that resolvins RvE1, RvD1, and LXA4alone stimulate [Ca2+]i and secretion. In these experiments, the resolvins were added (with no other additions) and [Ca2+]i or secretion were measured. The second role is the resolution of inflammation and as such they inhibit histamine- and leukotriene-stimulated increase in [Ca2+]i and secretion. This was demonstrated by incubation of goblet 740 Y-P for 30 min with resolvins prior to addition of either histamine or leukotrienes (Dartt et al., 2011; Li et al., 2013). In summary, RvE1 stimulates conjunctival goblet cells to secrete high molecular weight glycoconjugates including MUC5AC secretion by increasing [Ca2+]i. which in turns activates the PLC, PLD and PLA2 signaling pathways. Previous results have shown that RvE1, like RvD1 and LXA4, counter-regulate inflammatory mediator induced glycoconjugate secretion (Dartt et al., 2011; Hodges et al., 2016a). RvE1, RvD1 and LXA4 appear to act in similar ways to regulate glycoconjugate mucin secretion during physiological conditions using different GPCR to evoke intracellular signals. We conclude that RvE1, as well as other SPMs, help to maintain stable, normal glycoconjugate mucin production in the ocular surface. Thus, RvE1 may be useful both to maintain ocular surface health and as a treatment of ocular surface inflammatory diseases.
Funding This work was supported by The Norwegian Research Council to M.L., National Institute of Health GrantEY019470 to D.A.D, and R01GM038765 to C.N.S.
Acknowledgments