Cannabidiol alleviates suture-induced corneal pathological angiogenesis and inflammation by inducing myeloid-derived suppressor cells
- Int Immunopharmacol. 2024 Jun 7:137:112429. doi: 10.1016/j.intimp.2024.112429.
- 1. Eye Hospital, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, Heilongjiang, China.
- 2. Southwest Hospital/Southwest Eye Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China.
- 3. Eye Hospital, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, Heilongjiang, China; Key Laboratory of Ischemia-reperfusion, Harbin Medical University, Ministry of Education, Harbin 150001, Heilongjiang, China; Experimental Animal Centre, the Second Affiliated Hospital, Harbin Medical University, Harbin 150001, Heilongjiang, China.
- 4. Eye Hospital, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, Heilongjiang, China. Electronic address: [email protected].
- 5. Eye Hospital, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, Heilongjiang, China. Electronic address: [email protected].
Background: Currently, no perfect treatment for neovascularization and lymphangiogenesis exist, and each treatment method has its complications and side effects. This study aimed to investigate the anti-angiogenic and anti-inflammatory effects of cannabidiol and its mechanism of action.
Method: An in vivo corneal neovascularization (CNV) model was established using the suture method to investigate the inhibitory effects of CBD on suture-induced corneal inflammation, pathological blood vessel formation, and lymphangiogenesis. Additionally, the impact of CBD on immune cells was studied. In vitro methodologies, including cell sorting and co-culture, were employed to elucidate its mechanism of action.
Results: Compared with the CNV group, CBD can inhibit CNV, lymphangiogenesis, and inflammation induced via the suture method. In addition, CBD specifically induced CD45+CD11b+Gr-1+ cell upregulation, which significantly inhibited the proliferation of CD4+ T lymphocytes in vitro and exhibited a CD31+ phenotype, proving that they were myeloid-derived suppressor cells (MDSCs). We administered anti-Gr-1 to mice to eliminate MDSCs in vivo and found that anti-Gr-1 partially reversed the anti-inflammatory and angiogenic effects of CBD. Furthermore, we found that compared with MDSCs in the normal group, CBD-induced MDSCs overexpress peroxisome proliferator-activated receptor-gamma (PPAR-γ). Administering PPAR-γ inhibitor in mice almost reversed the induction of MDSCs by CBD, demonstrating the role of PPAR-γ in the function of CBD.
Conclusion: This study indicates that CBD may induce MDSCs upregulation by activating the nuclear receptor PPAR-γ, exerting anti-inflammatory, antiangiogenic, and lymphangiogenic effects, and revealing potential therapeutic targets for corneal neovascularization and lymphangiogenesis.