CANNABINOID RECEPTORS IN CONJUNCTIVAL EPITHELIUM: IDENTIFICATION AND FUNCTIONAL PROPERTIES.

IRIBARNE M, TORBIDONI V, JULIAN K, PRESTIFILIPPO JP, SINHA D, RETTORI V, BERRA A, SUBURO AM.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE

Association for Research in Vision and Ophthalmology

Lugar: Rockville; Año: 2008 vol. 49 p. 4535 - 4544

0146-0404

Purpose: Preservation of the ocular surface barrier requires a complex control of epithelial cell proliferation and inflammation mechanisms. The endocannabinoid system could be regulating those processes. Therefore, we explored the presence and properties of cannabinoid receptors (CB1 and CB2) in conjunctival epithelial cells. Methods: We used immunohistochemistry to detect CB1 and CB2 in normal mouse conjunctiva, human conjunctival cryosections and impression samples, and IOBA NHC cells, a human conjunctiva-derived cell line. The presence of CB1 and CB2 protein and transcripts was studied in IOBA-NHC cells by Western blot and RT-PCR, respectively. We also used this cell line to assay cannabinoid ligand-induced changes in cAMP levels, cell growth and Tumor Necrosis Factor-alpha (TNF-alpha)-induced activation of c-jun N terminal kinase (JNK) and Nuclear Factor-kappaB (NF-kappaB). Results: Mouse and human conjunctival epithelial cells displayed CB1 and CB2 protein and transcripts. Cannabinoid receptor activation decreased cAMP levels in IOBA-NHC cells, and specific CB1 and CB2 antagonists canceled this effect. Cannabinoid ligands also increased cell growth and blocked stress pathways activated by TNF-alpha in vitro. Conclusions: Cannabinoid receptors are present in mouse and human conjunctival cells. Functional responses, such as decrease of cAMP levels, proliferation and modulation of stress signaling pathways were mediated by CB1 and CB2 stimulation. Thus, these receptors might be involved in regulation of epithelial renewal and inflammatory processes at the ocular surface.