Data_Sheet_1_αB-Crystallin Alleviates Endotoxin-Induced Retinal Inflammation and Inhibits Microglial Activation and Autophagy.docx

αB-Crystallin, a member of the small heat shock protein (sHSP) family, plays an immunomodulatory and neuroprotective role by inhibiting microglial activation in several diseases. However, its effect on endotoxin-induced uveitis (EIU) is unclear. Autophagy may be associated with microglial activation, and αB-crystallin is involved in the regulation of autophagy in some cells. The role of αB-crystallin in microglial autophagy is unknown. This study aimed to explore the role of αB-crystallin on retinal microglial autophagy, microglial activation, and neuroinflammation in both cultured BV2 cells and the EIU mouse model. Our results show that αB-crystallin reduced the release of typical proinflammatory cytokines at both the mRNA and protein level, inhibited microglial activation in morphology, and suppressed the expression of autophagy-related molecules and the number of autophagolysosomes in vitro. In the EIU mouse model, αB-crystallin treatment alleviated the release of ocular inflammatory cytokines and the representative signs of inflammation, reduced the apoptosis of ganglion cells, and rescued retinal inflammatory structural and functional damage, as evaluated by optical coherence tomographic and electroretinography. Taken together, these results indicate that αB-crystallin inhibits the activation of microglia and supresses microglial autophagy, ultimately reducing endotoxin-induced neuroinflammation. In conclusion, αB-crystallin provides a novel and promising option for affecting microglial autophagy and alleviating symptoms of ocular inflammatory diseases.

αB-晶状蛋白，作为小热休克蛋白家族（sHSP）的一员，通过抑制多种疾病中的小胶质细胞激活，发挥着免疫调节和神经保护的作用。然而，其在内毒素诱导的葡萄膜炎（EIU）中的作用尚不明确。自噬可能与小胶质细胞激活相关联，而αB-晶状蛋白参与某些细胞中自噬的调节。αB-晶状蛋白在小胶质细胞自噬中的作用尚不为人所知。本研究旨在探讨αB-晶状蛋白对培养的BV2细胞和EIU小鼠模型中视网膜小胶质细胞自噬、小胶质细胞激活和神经炎症的作用。我们的结果显示，αB-晶状蛋白在mRNA和蛋白水平上降低了典型促炎细胞因子的释放，抑制了小胶质细胞在形态上的激活，并在体外抑制了自噬相关分子的表达和自噬溶酶体的数量。在内毒素诱导的葡萄膜炎小鼠模型中，αB-晶状蛋白治疗减轻了眼部炎症细胞因子的释放和炎症的代表性症状，减少了节细胞的凋亡，并通过光学相干断层扫描和电生理视网膜电图评估，挽救了视网膜炎症的结构和功能损伤。综合这些结果，表明αB-晶状蛋白抑制了小胶质细胞的激活和自噬，最终降低了内毒素诱导的神经炎症。总之，αB-晶状蛋白为影响小胶质细胞自噬和缓解眼部炎症疾病症状提供了新颖且具有潜力的选择。