上皮间充质转化在增生性玻璃体视网膜病变发病机制中的潜在作用

Potential effect of epithelial mesenchymal transition in pathogenesis of proliferative vitreoretinopathy

增生性玻璃体视网膜病变(proliferative vitreoretinopathy,PVR)是一种以纤维化为特点具有潜在致盲性的眼科并发症,其病理改变是产生视网膜前膜(epiretinal membranes,ERMs)。ERMs是一种纤维增殖膜,在视网膜前后表面及玻璃体内形成,当其收缩后导致PVR的发生,最终形成视网膜皱褶和牵引视网膜脱离(tractional retinal detachment,TRD)。多种细胞类型在ERMs中已被确定,视网膜色素上皮(retinal pigment epithelium,RPE)在PVR的病理生理学中至关重要。大量的临床和实验证据研究表明,RPE细胞采用了成纤维细胞表型发生了上皮间充质转化(epithelial-mesenchymal transition,EMT),并且还涉及大量的细胞因子、转录因子。EMT的特点是细胞间黏附和顶面-底侧细胞极性的缺失,这增加了细胞的移行性。由此产生的细胞能够通过细胞外基质迁移和转移。细胞间黏附由连接复合体维系着,它们在维护RPE细胞表型方面起重要作用,其通过激活一些信号通路及转录因子破坏这些连接复合体并导致EMT的发生。经过EMT过程后,转化生长因子-β使RPE细胞进一步分化为肌成纤维细胞。源自RPE细胞的成纤维细胞和肌成纤维细胞可以通过细胞迁移、增殖,导致ERMs的形成,这在PVR的病程发展中起着关键性作用。

Proliferative vitreoretinopathy(PVR)is an ocular complication characterized by fibrosis and potentially blinding.The pathological changes are the production of the epiretinal membranes(ERMs).ERMs is a kind of fibrous membrane,which is formed in the front and back of the retina and in the vitreous body.When it contractions,it causes the occurrence of PVR and eventually forms retinal folds and traction retinal detachments(TRD).Multiple cell types have been identified in ERMs.Retinal pigment epithelium is very important in the pathophysiology of PVR.A large number of clinical and experimental evidence studies have shown that RPE cells have undergone epithelial mesenchymal transition(EMT)to adopt fibroblast phenotype,and also involve a large number of cytokines and transcription factors.EMT is characterized by loss of cell-cell adhesion and apical-basal cell polarit,which enhances cell migration.The resulting cells can migrate through extracellular matrix.Cell-cell adhesions is maintained by the junction complex,which plays an important role in maintaining the phenotype of RPE cells.Furthermore,disruption of these junctional complexes results in EMT via activation of signaling pathways as well as transcription factors.Upon EMT,TGF-βfurther differentiated RPE cells into myofibroblasts.Fibroblasts and myofibroblasts derived from RPE cells can lead to the formation of ERMs through cell migration and proliferation,which plays a critical role in the development of PVR.