坏死性凋亡在眼科的研究进展及其抑制剂的临床应用

Research progress of necroptosis in ophthalmology and clinical application of its inhibitors

坏死性凋亡是近十几年来细胞死亡领域的重大发现。目前在眼科领域,已经从角膜疾病、青光眼、视网膜疾病等方向发现了坏死性凋亡通路的激活。除了针对受体相互作用蛋白1(RIP1)靶点的Necrostatin-1(Nec-1)坏死性凋亡抑制剂之外,受体相互作用蛋白3(RIP3)抑制剂GSK2399872A(GSK872)和针对混合谱系激酶结构域样蛋白(MLKL)靶点的新型抑制剂TC13172等药物在细胞死亡机制方面取得了重大突破。目前,坏死性凋亡抑制剂已经在眼科的多种疾病模型中证明了其保护作用。本文重点概述了坏死性凋亡的分子机制及其抑制剂在眼科中的研究成果,探讨坏死性凋亡作为眼科疾病治疗新靶点的潜力,并对其在眼科领域的进一步研究提出建议。

Necroptosis is a major discovery in the field of cell death in recent decades.At present,in the field of ophthalmology,the activation of necroptosis pathway has been found from corneal diseases,glaucoma,reti⁃nal diseases and so on.In addition to Necrostatin-1(Nec-1),a necroptosis inhibitor targeting receptor-interacting protein1(RIP1),drugs such as GSK2399872A(GSK872),a receptor-interacting protein3(RIP3)inhibitor,and TC13172,a novel inhibitor targeting mixed lineage kinase domain-like protein(MLKL),have made major break⁃throughs in cell death mechanisms.Currently in the field of ophthalmology,necroptosis inhibitors have demon⁃strated their protective effects in a variety of disease models.This article focuses on the molecular mechanism of necroptosis and the research results of its inhibitors in ophthalmology,discusses the potential of necroptosis as a new target for the treatment of ophthalmic diseases,and puts forward suggestions for its further research in the field of ophthalmology.