Wan Mi-Mi, Fu Zhang-Yitian, Jin Tuo, Wang Zhuo-Yuan, Sun Xin-Yi, Gao Wei-Ping
Department of Ophthalmology, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
Department of Ophthalmology, Kunshan Hospital of Chinese Medicine, Suzhou, China.
Purinergic Signal. 2024 Mar 11. doi: 10.1007/s11302-024-09991-0.
Dry eye (DE) is a prevalent ocular surface disease in patients with type 2 diabetes (T2DM). However, current medications are ineffective against decreased sensation on the ocular surface. While electroacupuncture (EA) effectively alleviates decreased sensation on ocular surface of DE in patients with T2DM, the neuroprotective mechanism remains unclear. This study explored the pathogenesis and therapeutic targets of T2DM-associated DE through bioinformatics analysis. It further investigated the underlying mechanism by which EA improves decreased sensation on the ocular surface of DE in rats with T2DM. Bioinformatic analysis was applied to annotate the potential pathogenesis of T2DM DE. T2DM and DE was induced in male rats. Following treatment with EA and fluorometholone, comprehensive metrics were assessed. Additionally, the expression patterns of key markers were studied. Key targets such as NLRP3, Caspase-1, and NOD-like receptor signaling may be involved in the pathogenesis of T2DM DE. EA treatment improved ocular measures. Furthermore, EA potently downregulated P2XR, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1 expression within the trigeminal ganglion and spinal trigeminal nucleus caudalis. Targeted P2XR antagonist (A-438079) and agonist (BzATP) employed as controls to decipher the biochemistry of the therapeutic effects of EA showed an anti-inflammatory effect with A-438079, while BzATP blocked the anti-inflammatory effect of EA. EA relieved DE symptoms and attenuated inflammatory damage to sensory nerve pathways in T2DM rats with DE. These findings suggest a crucial role of EA inhibition of the P2XR-NLRP3 inflammatory cascade to provide these benefits.
干眼（DE）是2型糖尿病（T2DM）患者中一种常见的眼表疾病。然而，目前的药物对眼表感觉减退无效。虽然电针（EA）能有效缓解T2DM患者DE眼表的感觉减退，但其神经保护机制仍不清楚。本研究通过生物信息学分析探讨了T2DM相关性DE的发病机制和治疗靶点。进一步研究了EA改善T2DM大鼠DE眼表感觉减退的潜在机制。应用生物信息学分析来注释T2DM DE的潜在发病机制。在雄性大鼠中诱导T2DM和DE。在用EA和氟米龙治疗后，评估综合指标。此外，研究了关键标志物的表达模式。关键靶点如NLRP3、半胱天冬酶 -1和NOD样受体信号通路可能参与T2DM DE的发病机制。EA治疗改善了眼部指标。此外，EA显著下调三叉神经节和三叉神经尾侧核内的P2XR、NLRP3、含CARD的凋亡相关斑点样蛋白（ASC）和半胱天冬酶 -1的表达。作为对照使用靶向P2XR拮抗剂（A - 438079）和激动剂（BzATP）来解读EA治疗效果的生物化学机制，结果显示A - 438079具有抗炎作用，而BzATP阻断了EA的抗炎作用。EA缓解了T2DM合并DE大鼠的DE症状，并减轻了感觉神经通路的炎性损伤。这些发现表明EA抑制P2XR - NLRP3炎性级联反应发挥了关键作用从而带来这些益处。
