Department of Anatomy, Histology and Embryology, School of Medicine, University of Patras, GR‑26504 Rio, Greece.
Department of Ophthalmology, School of Medicine, University of Patras, GR‑26504 Rio, Greece.
Mol Med Rep. 2017 Oct;16(4):5285-5293. doi: 10.3892/mmr.2017.7246. Epub 2017 Aug 14.
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.
大麻素作为多靶点介质,可激活大麻素受体和瞬时受体电位香草酸 (TRPV) 通道。有证据表明,当它们共表达时,大麻素受体和 TRPV 通道之间存在功能相互作用。人结膜广泛表达大麻素受体 1 型 (CB1)、CB2 和 TRPV 通道。本研究旨在研究眼表面病变翼状胬肉中大麻素受体 (CB1 和 CB2) 和 TRPV 通道的表达谱。使用特定抗体对原发性和复发性翼状胬肉样本的半连续石蜡包埋切片进行免疫组织化学检查。94%、78%、96%、73%和 80%的翼状胬肉上皮层分别显示 CB1、CB2、TRPV1、TRPV2 和 TRPV3 细胞质免疫反应性。所有翼状胬肉病例的上皮层(100%)均显示强烈的、主要为核的 TRPV4 免疫定位。在翼状胬肉基质中,散在的细胞表现出强烈的 CB2 免疫反应性,而血管内皮细胞对大麻素受体和所有 TRPV 通道均呈免疫阳性。上皮细胞免疫组织化学发现的定量分析表明,CB1 在结膜中的表达水平明显高于原发性翼状胬肉(P=0.04),但 CB2 则不然(P>0.05)。此外,CB1 和 CB2 在原发性翼状胬肉中的表达水平明显高于复发性翼状胬肉(P=0.01)。此外,CB1 表达水平与原发性翼状胬肉中的 CB2 表达水平呈显著正相关(P=0.005),但与复发性翼状胬肉无关(P>0.05)。TRPV 通道表达水平在原发性或复发性翼状胬肉与结膜组织之间无显著差异(P>0.05)。TRPV1 和 TRPV3 表达水平之间存在显著相关性(P<0.001),与翼状胬肉的复发无关。最后,在翼状胬肉样本中检测到 TRPV 通道的表达明显高于大麻素受体的表达水平(P<0.001)。原发性和复发性翼状胬肉中大麻素受体的差异表达结合 TRPV 通道的存在表明,这些大麻素靶点可能在翼状胬肉的潜在机制中发挥作用。