Son Myeongjoo, Nagahawatta Dineth Pramuditha, Jo Hang-Chan, Jeon You-Jin, Ryu Bomi, Kim Dae Yu
Department of Anatomy & Cell Biology, School of Medicine, Kangwon National University, Chuncheon, 24341, Republic of Korea.
Brain Health Research Laboratory, Institute of Medical Science, Kangwon National University College of Medicine, Chuncheon, 24341, Republic of Korea.
Heliyon. 2025 Feb 5;11(4):e42475. doi: 10.1016/j.heliyon.2025.e42475. eCollection 2025 Feb 28.
Müller gliosis is a complex process that impairs the ability of retinal Müller glial cells to respond to various forms of retinal injury or disease, leading to retinal damage. Blue light (BL) exposure is a known cause of retinal damage. In this study, we aimed to investigate the potential of DPHC in inhibiting Müller gliosis in models of BL-exposure. We conducted in silico binding analysis to evaluate the binding of DPHC to CXCR4. Then, we developed in vitro and experimental models to assess the effects of DPHC and BL exposure on Müller gliosis using MIO-M1 cells and zebrafish. Our findings show that DPHC can suppress the Müller gliosis process in BL-exposed MIO-M1 cells in vitro and in BL-exposed zebrafish . In silico molecular docking, we identified CXCR4 as the target of active site 1 of DPHC. In BL-exposed MIO-M1 cells, DPHC inhibited CXCR4 activity and altered the expression of Müller gliosis markers and NF-κB-related ERK and AKT signaling. In BL-exposed zebrafish, DPHC prevented retinal thickness reduction and inhibited CXCR4 expression and retinal cell apoptosis. This study suggests that DPHC could be a potential therapeutic agent for retinal diseases involving Müller gliosis. By inhibiting CXCR4 activity, DPHC downregulates the ERK/AKT/NF-κB pathway, reducing retinal cell apoptosis and altered expression of Müller gliosis markers. These findings highlight the potential of natural bioactive compounds for treating various diseases, and further research should investigate the therapeutic potential of DPHC and its derivatives.
穆勒胶质细胞增生是一个复杂的过程，它会损害视网膜穆勒胶质细胞对各种形式的视网膜损伤或疾病作出反应的能力，从而导致视网膜损伤。蓝光暴露是已知的视网膜损伤原因。在本研究中，我们旨在研究二氢辣椒素（DPHC）在蓝光暴露模型中抑制穆勒胶质细胞增生的潜力。我们进行了计算机模拟结合分析，以评估DPHC与CXCR4的结合。然后，我们建立了体外和实验模型，使用MIO-M1细胞和斑马鱼评估DPHC和蓝光暴露对穆勒胶质细胞增生的影响。我们的研究结果表明，DPHC可以在体外抑制蓝光暴露的MIO-M1细胞以及蓝光暴露的斑马鱼中的穆勒胶质细胞增生过程。在计算机模拟分子对接中，我们确定CXCR4是DPHC活性位点1的靶点。在蓝光暴露的MIO-M1细胞中，DPHC抑制CXCR4活性，并改变穆勒胶质细胞增生标志物以及与NF-κB相关的ERK和AKT信号的表达。在蓝光暴露的斑马鱼中，DPHC可防止视网膜厚度减小，并抑制CXCR4表达和视网膜细胞凋亡。本研究表明，DPHC可能是一种用于治疗涉及穆勒胶质细胞增生的视网膜疾病的潜在治疗药物。通过抑制CXCR4活性，DPHC下调ERK/AKT/NF-κB通路，减少视网膜细胞凋亡并改变穆勒胶质细胞增生标志物的表达。这些发现凸显了天然生物活性化合物在治疗各种疾病方面的潜力，进一步的研究应探讨DPHC及其衍生物的治疗潜力。
