Effects of hyperosmolarity on annexin A1 on ocular surface epithelium in vitro.

Osmotic stress is an important challenge to cell function. Dry eye pathology is characterized by elevated tear film osmolarity as consequence of decreased tear secretion and/or increased evaporation. Dry eye pathogenesis is not completely clarified. However, it is known that tear hyperosmolarity induces NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-cointaining 3) inflammasome activation and inflammatory mediators release that leads to ocular surface damage. Annexin A1 is a protein involved in anti-inflammatory or pro-resolution actions in different tissues while its presence and biological role on ocular surface has been scarcely examined. In this study, potential changes in annexin A1 protein expression and secretion on the ocular surface after exposure to hyperosmolar conditions were evaluated. In addition, considering the significant role of inflammation in dry eye pathology, the potential anti-inflammatory activity of Ac2-26, an annexin A1 peptide mimicking its N-terminus, was assessed. Cytosolic and membrane staining was detected for annexin A1 in corneal and conjunctival epithelial cells. A native form of annexin A1 together with a truncated form were detected by western blot analysis. Under hyperosmotic conditions increased protein levels of intracellular and secreted annexin A1 as well as higher expression of its receptor Fpr2 (formyl peptide receptor type 2) were found. Treatment with mimetic peptide Ac2-26 ameliorated NLRP3 activation and interleukin 1β (IL-1β) release triggered by elevated osmolarity in corneal and conjunctival epithelial cells. These findings suggest a potential role of annexin A1 and its mimetic peptide modulating key inflammatory events associated to dry eye.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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