The First Clinical Medical College, Lanzhou University, Lanzhou 730000, The People's Republic of China.
Department of Endocrinology, First Hospital of Lanzhou University, Lanzhou, Gansu 730000, The People's Republic of China; Gansu Province Clinical Research Center for Endocrine Disease, Gansu 730000, The People's Republic of China.
Biochem Pharmacol. 2023 Jun;212:115569. doi: 10.1016/j.bcp.2023.115569. Epub 2023 Apr 25.
Diabetic retinopathy (DR) is a common diabetic microvascular complication and the main cause of vision loss in working-aged people. The NLRP3 inflammasome is a cytosolic multimeric complex that plays a significant role in innate immunity. After sensing injury, the NLRP3 inflammasome induces inflammatory mediator secretion and triggers a form of inflammatory cell death known as pyroptosis. Studies over the past five years have shown increased expression of NLRP3 and related inflammatory mediators in vitreous samples from DR patients at different clinical stages. Many NLRP3-targeted inhibitors have shown great antiangiogenic and anti-inflammatory effects in diabetes mellitus models, suggesting that the NLRP3 inflammasome is involved in the progression of DR. This review covers the molecular mechanisms of NLRP3 inflammasome activation. Furthermore, we discuss the implications of the NLRP3 inflammasome in DR, including the induction of pyroptosis and inflammation and the promotion of microangiopathy and retinal neurodegeneration. We also summarize the research progress on targeting the NLRP3 inflammasome in DR therapeutics with the expectation of providing new insights into DR progression and treatment.
糖尿病性视网膜病变（DR）是一种常见的糖尿病微血管并发症，也是工作年龄段人群视力丧失的主要原因。NLRP3 炎性小体是一种细胞溶质多聚体复合物，在先天免疫中发挥重要作用。在感知损伤后，NLRP3 炎性小体诱导炎症介质的分泌，并引发一种称为细胞焦亡的炎症细胞死亡形式。过去五年的研究表明，在不同临床阶段的 DR 患者的玻璃体样本中，NLRP3 及相关炎症介质的表达增加。许多 NLRP3 靶向抑制剂在糖尿病模型中显示出强大的抗血管生成和抗炎作用，提示 NLRP3 炎性小体参与了 DR 的进展。本综述涵盖了 NLRP3 炎性小体激活的分子机制。此外，我们还讨论了 NLRP3 炎性小体在 DR 中的作用，包括诱导细胞焦亡和炎症以及促进微血管病变和视网膜神经退行性变。我们还总结了 NLRP3 炎性小体在 DR 治疗中的靶向研究进展，以期为 DR 的进展和治疗提供新的思路。
