2. Academic Validation
  3. Cannabidiol alleviates suture-induced corneal pathological angiogenesis and inflammation by inducing myeloid-derived suppressor cells

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.
Chaoqun Wei 1,  Yu Mi 2,  Liyao Sun 1,  Jialin Luo 3,  Jiayue Zhang 3,  Yi Gao 1,  Xiaohan Yu 1,  Hongyan Ge 4,  Ping Liu 5
Affiliations

Affiliations

  • 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: gehongyan@hrbmu.edu.cn.
  • 5 Eye Hospital, the First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, Heilongjiang, China. Electronic address: liuping@hrbmu.edu.cn.
PMID: 38851157 DOI: 10.1016/j.intimp.2024.112429
Abstract

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.

Keywords

Cannabidiol; Corneal neovascularization; Corneal new lymphatic vessels; Inflammation; Myeloid suppressor cells; Natural product.

Figures
Products
  • Cat. No.
    Product Name
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  • HY-16578
    99.79%, PPARγ Antagonist