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Zhao-Hui Song, Jingrui Wang, Alyssa S Laun, Deming Sun, Henry J Kaplan, Hui Shao; The upregulation of GPR3 during experimental autoimmune uveitis (EAU) and inhibition of pathogenic uveitogenic T cells by GPR3 ligand cannabidiol (CBD). Invest. Ophthalmol. Vis. Sci. 2019;60(9):783. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Cannabidiol (CBD) is a major, non-psychoactive component of marijuana. This study is aimed at investigating the expression and function of G protein-coupled receptor 3 (GPR3), a newly identified molecular target for CBD, in the immune system and the eye.
Western blot and flow cytometry analysis were used to investigate the expression of GPR3 in mouse tissues and primary cells. Enzyme linked immunosorbant assay (ELISA) was used to measure cytokine levels in the supernatants of cell cultures. EAU in C57BL/6J (B6) mice was induced by the mixture of human interphotoreceptor retinoid binding protein (IRBP) peptide 1-20 and complete Freund’s adjuvant (CFA).
GPR3 is expressed at low levels in the spleen, and barely detectable in the eye of naïve mice. The GPR3 expression, however, is drastically increased in both tissues during EAU. T cells and antigen presenting cells (APCs) - B cells and dendritic cells (DCs), express GPR3. In addition, GPR3 expression was detected in ocular glial cells. Furthermore, CBD was found to inhibit pro-inflammatory cytokine IL-6 release from astrocytes stimulated by lipopolysaccharide (LPS) (p<0.05). In addition, CBD inhibited uveitogenic T cell proliferation, and Th1/Th17 cell differentiation (p<0.05).
Functional GPR3 proteins are expressed in the immune system and the eye during intraocular inflammation. This indicates that GPR3 may play an important role in the development of autoimmune uveitis. Our data also points to the potential of CBD as a treatment for intraocular inflammation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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