程序性死亡受体1及其配体1在眼部疾病发病机制中的研究进展

Research progress of programmed cell death 1 and its receptor programmed cell death 1 ligand 1 in the pathogenesis of eye diseases

程序性死亡受体1(PD-1)是近年来发现的一种重要的负性共刺激分子,诱导性表达于T、B细胞表面,在调控细胞免疫应答及免疫耐受等过程中起着重要的作用。PD-1与程序性死亡-配体1(PD-L1)结合后通过募集磷酸化的SHP2减弱下游如PI3K/Akt和ERK等信号通路的传导,进而抑制T细胞的增生和细胞因子的产生,抑制免疫应答,参与大量炎症性疾病的发生和发展。PD-1在眼科领域的研究尚处于起步阶段,除参与眼科炎症性疾病如葡萄膜炎、交感性眼炎、变态反应性结膜炎等疾病的发病以外,也参与角膜移植排斥反应、视神经损伤、视神经脊髓炎、糖尿病视网膜病变、甲状腺相关眼病及黑色素瘤等疾病,因而阻断PD-1及其配体PD-L1之间的相互作用有可能成为治疗眼部肿瘤、炎症、免疫性、退变性疾病的潜在的靶点。本文就PD-1及其配体PD-L1在眼部疾病发病中作用的最新研究进展作一综述。

Programmed cell death 1(PD-1)is an important negative costimulatory molecule discovered in recent years,which is expressed on the surface of T and B cells and plays an important role in the regulation of cellular immune response and immune tolerance.After the combination of PD-1 and its receptor programmed cell death 1 ligand 1(PD-L1),negative regulatory signals are transmitted to suppress the immune response.Under the activation of stimulating factors,PD-1 and PD-L1 are combined to weaken the conduction of downstream signaling pathways such as PI3K/Akt and ERK through recruitment of phosphorylated SHP2,thereby inhibiting the proliferation of T cells and the production of cytokines,inhibiting the immune response and participating in the occurrence and development of a large number of inflammatory diseases.PD-1 in the field of ophthalmology research is still in its infancy.As far as we know,PD-1 participates in ocular inflammatory diseases such as uveitis,sympathetic ophthalmia,allergic conjunctivitis,also is involved in corneal transplant rejection,optic nerve crush injury and optic myelitis,diabetic retinopathy,thyroid related ophthalmopathy,melanoma and other diseases,thus preventing the interactions between PD-1 and its receptor PD-L1 may become a new potential target for the treatment of ocular tumor,inflammation,autoimmune and neurodegeneration disease.In this article,the latest research progress of PD-1 and its receptor PD-L1 in the pathogenesis of ocular diseases were reviewed.