Immunolocalization of cannabinoid receptor type 1 and CB2 cannabinoid receptors, and transient receptor potential vanilloid channels in pterygium

Abstract

Cannabinoids, as multi-target mediators, activate cannabinoid receptors and transient receptor potential vanilloid (TRPV) channels. There is evidence to support a functional interaction of cannabinoid receptors and TRPV channels when they are coexpressed. Human conjunctiva demonstrates widespread cannabinoid receptor type 1 (CB1), CB2 and TRPV channel localization. The aim of the present study was to investigate the expression profile for cannabinoid receptors (CB1 and CB2) and TRPV channels in pterygium, an ocular surface lesion originating from the conjunctiva. Semi-serial paraffin-embedded sections from primary and recurrent pterygium samples were immunohistochemically examined with the use of specific antibodies. All of the epithelial layers in 94, 78, 96, 73 and 80% of pterygia cases, exhibited CB1, CB2, TRPV1, TRPV2 and TRPV3 cytoplasmic immunoreactivity, respectively. The epithelium of all pterygia cases (100%) showed strong, mainly nuclear, TRPV4 immunolocalization. In the pterygium stroma, scattered cells demonstrated intense CB2 immunoreactivity, whereas vascular endothelial cells were immunopositive for the cannabinoid receptors and all TRPV channels. Quantitative analyses of the immunohistochemical findings in epithelial cells demonstrated a significantly higher expression level in conjunctiva compared with primary pterygia (P=0.04) for CB1, but not for CB2 (P>0.05). Additionally, CB1 and CB2 were significantly highly expressed in primary pterygia (P=0.01), compared with recurrent pterygia. Furthermore, CB1 expression levels were significantly correlated with CB2 expression levels in primary pterygia (P=0.005), but not in recurrent pterygia (P>0.05). No significant difference was detected for all TRPV channel expression levels between pterygium (primary or recurrent) and conjunctival tissues (P>0.05). A significant correlation between the TRPV1 and TRPV3 expression levels (P<0.001) was detected independently of pterygium recurrence. Finally, TRPV channel expression was identified to be significantly higher than the expression level of cannabinoid receptors in the pterygium samples (P<0.001). The differentiated expression of cannabinoid receptors in combination with the presence of TRPV channels, in primary and recurrent pterygia, imply a potential role of these cannabinoid targets in the underlying mechanisms of pterygium.

Alteration of expression pattern of transient receptor potential vanilloid 2 and transient receptor potential vanilloid 3 in ocular surface neoplasm

“…A study indicated a reduction of TRPV1, TRPV2, and TRPV4 expression levels and an increased level of TRPV3 expression in epithelium of a primary pterygium as compared with normal conjunctival. [ 17 ] The findings in the pterygial epithelium were not identical to our data, although the exact reason, for example, racial difference, is to be explored. These authors report that the expression of TRPV3 was more marked in the pterygial epithelium as compared with a healthy conjunctival epithelium that coincides with our data.…”

“…This tissue is composed of stratified epithelium and stroma and an innermost endothelial single-cell layer. [ 12 13 14 15 16 ] Although the expression pattern of TRP family members in healthy cornea and conjunctiva as well as pterygium was described,[ 17 18 ] there are no available reports describing their expression pattern in ocular surface neoplastic lesions.…”

Expression Profiling of the Transient Receptor Potential Vanilloid (TRPV) Channels 1, 2, 3 and 4 in Mucosal Epithelium of Human Ulcerative Colitis

“…Control slides were invariably negative for immunostaining. Renal tissue was used as positive control for TRPV1, TRPV3, and TRPV4 antibodies and ophthalmic pterygium for TRPV2 antibody [ 42 , 43 ].…”

CannabinEYEds: The Endocannabinoid System as a Regulator of the Ocular Surface Nociception, Inflammatory Response, Neovascularization and Wound Healing

“…Similarly, Assimakopoulou et al described an intense immunostaining for CB1r and CB2r in all tissue layers of human pterygium, in a case series including 32 eyes of 32 patients. In particular, they described a strong and moderate granular cytoplasmic immunoreactivity for CB1r and CB2r in the basal and suprabasal layers, respectively [ 25 ].…”