Cannabinoid-induced chemotaxis in bovine corneal epithelial cells

Natalia Murataeva, Shimin Li, Olivia Oehler, Sally Miller, Amey Dhopeshwarkar, Sherry Shu Jung Hu, Joseph A. Bonanno, Heather Bradshaw, Ken Mackie, Douglas McHugh, Alex Straiker

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)

Abstract

PURPOSE. Cannabinoid CB1receptors are found in abundance in the vertebrate eye, with most tissue types expressing this receptor. However, the function of CB1 receptors in corneal epithelial cells (CECs) is poorly understood. Interestingly, the corneas of CB1 knockout mice heal more slowly after injury via a mechanism proposed to involve protein kinase B (Akt) activation, chemokinesis, and cell proliferation. The current study examined the role of cannabinoids in CEC migration in greater detail. METHODS. We determined the role of CB1 receptors in corneal healing. We examined the consequences of their activation on migration and proliferation in bovine CECs (bCECs). We additionally examined the mRNA profile of cannabinoid-related genes and CB1 protein expression as well as CB1 signaling in bovine CECs. RESULTS. We now report that activation of CB1 with physiologically relevant concentrations of the synthetic agonist WIN55212-2 (WIN) induces bCEC migration via chemotaxis, an effect fully blocked by the CB1 receptor antagonist SR141716. The endogenous agonist 2- arachidonoylglycerol (2-AG) also enhances migration. Separately, mRNA for most cannabinoidrelated proteins are present in bovine corneal epithelium and cultured bCECs. Notably absent are CB2 receptors and the 2-AG synthesizing enzyme diglycerol lipase-a (DAGLa). The signaling profile of CB1 activation is complex, with inactivation of mitogen-activated protein kinase (MAPK). Lastly, CB1 activation does not induce bCEC proliferation, but may instead antagonize EGF-induced proliferation. CONCLUSIONS. In summary, we find that CB1-based signaling machinery is present in bovine cornea and that activation of this system induces chemotaxis.

Original languageEnglish
Pages (from-to)3304-3313
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number5
DOIs
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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