PDF(Pubmed)
Abstract：
Inherited retinal dystrophies (IRDs) as well as genetically complex retinal phenotypes represent a heterogenous group of ocular diseases, both on account of their phenotypic and genotypic characteristics. Therefore, overlaps in clinical features often complicate or even impede their correct clinical diagnosis. Deciphering the molecular basis of retinal diseases has not only aided in their disease classification but also helped in our understanding of how different molecular pathologies may share common pathomechanisms. In particular, these relate to dysregulation of two key processes that contribute to cellular integrity, namely extracellular matrix (ECM) homeostasis and inflammation. Pathological changes in the ECM of Bruch\'s membrane have been described in both monogenic IRDs, such as Sorsby fundus dystrophy (SFD) and Doyne honeycomb retinal dystrophy (DHRD), as well as in the genetically complex age-related macular degeneration (AMD) or diabetic retinopathy (DR). Additionally, complement system dysfunction and distorted immune regulation may also represent a common connection between some IRDs and complex retinal degenerations. Through highlighting such overlaps in molecular pathology, this review aims to illuminate how inflammatory processes and ECM homeostasis are linked in the healthy retina and how their interplay may be disturbed in aging as well as in disease.
摘要：
遗传性视网膜营养不良（IRD）以及遗传复杂的视网膜表型代表了一组异质性的眼部疾病，由于它们的表型和基因型特征。因此,临床特征的重叠常常使其复杂甚至妨碍其正确的临床诊断。解密视网膜疾病的分子基础不仅有助于其疾病分类，而且有助于我们理解不同的分子病理学如何共享共同的病理机制。特别是,这些与两个有助于细胞完整性的关键过程的失调有关，即细胞外基质（ECM）稳态和炎症。布鲁赫膜ECM的病理变化已在两个单基因IRD中描述，如Sorsby眼底营养不良（SFD）和Doyne蜂窝状视网膜营养不良（DHRD），以及遗传复杂的年龄相关性黄斑变性（AMD）或糖尿病性视网膜病变（DR）。此外,补体系统功能障碍和免疫调节失调也可能代表了一些IRD与复杂视网膜变性之间的共同联系。通过突出分子病理学中的这种重叠，这篇综述旨在阐明炎症过程和ECM稳态在健康视网膜中是如何联系在一起的,以及它们之间的相互作用如何在衰老和疾病中受到干扰.
