Inflammation plays an important role in hypertensive retinal vascular injury and subsequent retinopathy. Monocyte chemotaxis via CXCL1-CXCR2 binding has been implicated in various cardiovascular diseases, but the function of CXCL1-CXCR2 signalling involved in retinopathy, which was investigated as angiotensin II (Ang II)-induced retinopathy, is unclear. In our study, we established a hypertensive retinopathy (HR) model by Ang II infusion (3000 ng/min/kg) for 3 weeks. To determine the involvement of CXCR2 signalling, we used CXCR2 knockout (KO) mice or C57BL/6J wild-type (WT) mice as experimental subjects. The mice were treated with a CXCL1 neutralizing antibody or SB225002 (the specific CXCR2 inhibitor). Our results showed that after Ang II treatment, the mRNA levels of CXCL1 and CXCR2 and the number of CXCR2⁺ inflammatory cells were significantly elevated. Conversely, unlike in the IgG control group, the CXCL1 neutralizing antibody greatly reduced the increase in central retinal thickness induced by Ang II infusion, arteriolar remodelling, superoxide production, and retinal dysfunction in WT mice. Furthermore, Ang II infusion induced arteriolar remodelling, infiltration of Iba1⁺ macrophages, the production of oxidative stress, and retinal dysfunction, but the symptoms were ameliorated in CXCR2 KO mice and SB225002-treated mice. These protective effects were related to the reduction in the number of CXCR2⁺ immune cells, particularly macrophages, and the decrease in proinflammatory cytokine (IL-1β, IL-6, TNF-ɑ, and MCP-1) expression in Ang II-treated retinas. Notably, serum CXCL1 levels and the number of CXCR2⁺ monocytes/neutrophils were higher in HR patients than in healthy controls. In conclusion, this study provides new evidence that the CXCL1-CXCR2 axis plays a vital role in the pathogenesis of hypertensive retinopathy, and selective blockade of CXCL1-CXCR2 activation may be a potential treatment for HR.

炎症在高血压性视网膜血管损伤和随后的视网膜病变中起重要作用。通过 CXCL1-CXCR2 结合的单核细胞趋化性与各种心血管疾病有关，但 CXCL1-CXCR2 信号传导在视网膜病变中的功能，被研究为血管紧张素 II (Ang II) 诱导的视网膜病变，尚不清楚。在我们的研究中，我们通过输注 Ang II (3000 ng/min/kg) 3 周建立了高血压视网膜病变 (HR) 模型。为了确定 CXCR2 信号传导的参与，我们使用 CXCR2 敲除 (KO) 小鼠或 C57BL/6J 野生型 (WT) 小鼠作为实验对象。用 CXCL1 中和抗体或 SB225002（特异性 CXCR2 抑制剂）治疗小鼠。我们的结果表明，经过 Ang II 处理后，CXCL1 和 CXCR2 的 mRNA 水平以及 CXCR2 ^+的数量炎症细胞明显升高。相反，与 IgG 对照组不同，CXCL1 中和抗体大大降低了 WT 小鼠中由 Ang II 输注、小动脉重塑、超氧化物产生和视网膜功能障碍引起的中央视网膜厚度的增加。此外，Ang II 输注诱导小动脉重塑、Iba1 ⁺巨噬细胞浸润、氧化应激的产生和视网膜功能障碍，但在 CXCR2 KO 小鼠和 SB225002 处理的小鼠中症状得到改善。^{这些保护作用与 CXCR2 +}数量的减少有关免疫细胞，特别是巨噬细胞，以及 Ang II 处理的视网膜中促炎细胞因子（IL-1β、IL-6、TNF-ɑ 和 MCP-1）表达的降低。值得注意的是，HR 患者的血清 CXCL1 水平和 CXCR2 ⁺单核细胞/中性粒细胞的数量高于健康对照组。总之，本研究提供了新的证据，表明 CXCL1-CXCR2 轴在高血压视网膜病变的发病机制中起着至关重要的作用，选择性阻断 CXCL1-CXCR2 激活可能是 HR 的潜在治疗方法。