Hiscott P, Sheridan C, Magee R M, Grierson I
Department of Medicine, University of Liverpool, UK.
Prog Retin Eye Res. 1999 Mar;18(2):167-90. doi: 10.1016/s1350-9462(98)00024-x.
In their normal state, RPE cell are strongly adherent to Bruch's membrane. Certain pathological conditions such as retinal detachment cause an injury-type response (probably augmented or induced by the local accumulation of a variety of substances which modulate cell behaviour) in which RPE begin to dissociate from the membrane. This RPE-Bruch's membrane separation may be mediated by proteins with counter-adhesive properties and proteolytic enzymes, partly derived from the RPE themselves. Concomitant with the RPE disassociation, the cells begin to lose tertiary differentiation characteristics and gain macrophage-like features. When the "free" RPE arrive at the surface of the neuroretina, they may attach to or create a provisional matrix. Some of the cells adopt a fibroblast-like phenotype. This phenotype is similar to that of the dermal fibroblast during cutaneous wound repair and the fibroblastic RPE synthesise the types of matrix components found in healing skin wounds. Many of these molecules in turn further modulate the activities of the cells via several families of cell surface receptors, while the RPE continue to remodel the new matrix with a range of proteolytic enzymes. The resulting tissue (or membrane) has many of the features of a contractile scar and is the hallmark of the condition known as proliferative vitreoretinopathy (PVR). Thus the development of PVR, and the resulting tractional distortion of the neuroretina, appears to be dependent on RPE-matrix interactions. The interactions present a number of potential therapeutic targets for the management of the disorder.
在正常状态下，视网膜色素上皮（RPE）细胞与布鲁赫膜紧密相连。某些病理状况，如视网膜脱离，会引发一种损伤型反应（可能由多种调节细胞行为的物质在局部积聚增强或诱导），在此反应中，RPE细胞开始与布鲁赫膜分离。这种RPE细胞与布鲁赫膜的分离可能由具有抗黏附特性的蛋白质和蛋白水解酶介导，部分酶源自RPE细胞自身。伴随RPE细胞的分离，这些细胞开始丧失三级分化特征，并获得类似巨噬细胞的特性。当“游离”的RPE细胞到达神经视网膜表面时，它们可能附着于其上或形成临时基质。一些细胞呈现成纤维细胞样表型。这种表型类似于皮肤伤口修复过程中的真皮成纤维细胞，成纤维细胞样的RPE细胞能合成愈合皮肤伤口中发现的基质成分类型。这些分子中的许多反过来又通过几类细胞表面受体进一步调节细胞活性，而RPE细胞则继续用一系列蛋白水解酶重塑新的基质。最终形成的组织（或膜）具有收缩性瘢痕的许多特征，是增殖性玻璃体视网膜病变（PVR）的标志。因此，PVR的发展以及由此导致的神经视网膜牵引性变形，似乎依赖于RPE细胞与基质的相互作用。这些相互作用为该疾病的治疗提供了许多潜在的治疗靶点。
