“Epithelial-mesenchymal transition (EMT) plays a significant role in conjunctival fibrosis-related pathologies and has emerged as a promising therapeutic target for managing conjunctival fibrosis.
Cannabidiol (CBD), a predominant non-psychoactive cannabinoid derived from the cannabis plant, has demonstrated antifibrotic effects in various extraorbital tissues. However, its influence on fibrosis-associated EMT in conjunctiva remains unexplored.
Given the ubiquitous expression of cannabinoid targets in ocular tissues, including the conjunctiva, and evidence suggesting that modulation of the endocannabinoid system ameliorates ocular pathologies, this study aimed to evaluate the effects of CBD on conjunctival EMT.
Cultured human conjunctival epithelial cells were stimulated with transforming growth factor-beta 1 (TGF-β1) to induce EMT.
CBD treatment effectively mitigated EMT-related changes induced by TGF-β1, including increased cell elongation and migration, reduced epithelial markers (E-cadherin and zonula occludens-1, and elevated mesenchymal markers (alpha-smooth muscle actin and fibronectin) and EMT-associated transcription factor Snail.
Furthermore, CBD suppressed TGF-β1-mediated Smad-2/3 phosphorylation and nuclear translocation. Treatment with a specific TGF-β/Smad pathway inhibitor (SB431542) yielded comparable results, suggesting that the inhibitory effects of CBD on EMT involve disruption of TGF-β/Smad signaling. Additionally, the EMT phenotype was associated with increased interleukin-6 (IL-6) secretion, which was also attenuated by CBD treatment.
This study confirms that CBD effectively prevents EMT and EMT-associated IL-6 secretion by targeting TGF-β/Smad signaling, highlighting its therapeutic potential in mitigating conjunctival fibrosis.”
https://pubmed.ncbi.nlm.nih.gov/41272047
“Our study revealed the anti-EMT effects of CBD in conjunctival epithelial cells, mediated through inhibition of the TGF-β-Smad-Snail axis. “
“Overall, as a compound with diverse properties, CBD may improve ocular surface pathologies resulting from inflammation and fibrosis through regulation of EMT and the associated inflammatory secretome, while also exerting neuroprotective and antinociceptive effects.”