Roque R S, Caldwell R B
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta 30912.
Exp Eye Res. 1991 Dec;53(6):787-98. doi: 10.1016/0014-4835(91)90115-u.
In the Royal College of Surgeons rat with inherited retinal dystrophy, vascularization of the retinal pigment epithelium (RPE) is preceded by migration and proliferation of Müller cell processes in the subretinal space where they contact the RPE. Later, RPE cells envelope subretinal vessels which have lost their perivascular Müller cell sheath. To characterize RPE cell changes and interactions in relation to glial and vascular transformations in retinal dystrophy, we used immunocytochemical techniques and antibodies against cytokeratin (CK) and glial fibrillary acidic protein (GFAP). Prior to the proliferation of Müller cell processes in the dystrophic retina, CK filaments in RPE cells formed a circumferential meshwork with intense cytoplasmic and perinuclear labeling as in control RPE cells. Following entry of Müller cell processes into the membranous debris zone and formation of RPE-Müller cell contact, RPE cells became pleomorphic and extended prominent apical processes in the debris zone. Some CK-reactive RPE cells detached from Bruch's membrane and migrated into the debris zone. Electron microscopic study showed extensive areas of close RPE-Müller cell contact at this time. Obvious junctional specializations of the plasma membranes were not seen but prominent tubulo-vesicular profiles occupied the cytoplasm of altered RPE and Müller cell processes. Following RPE vascularization, hypertrophic CK-positive cells surrounded blood vessels and accompanied them into the inner retina. Electron microscopic analysis showed that RPE-associated vessels were fenestrated and devoid of their perivascular glial sheath. Apparent proliferation of RPE cells and redistribution of CK filaments were observed. Our study shows that RPE cell alterations accompany Müller cell and vascular changes which result in altered RPE-Müller cell and RPE-endothelial cell relationships in the dystrophic rat retina. The altered relationships among RPE, Müller and endothelial cells may result in increased cellular interaction and promote proliferation and transformation of all three cells types in diseased retinas.
在患有遗传性视网膜营养不良的皇家外科学院大鼠中，视网膜色素上皮（RPE）的血管化之前，Müller细胞突起会在视网膜下间隙迁移和增殖，在此处它们与RPE接触。之后，RPE细胞包裹失去血管周围Müller细胞鞘的视网膜下血管。为了表征视网膜营养不良中与神经胶质和血管转变相关的RPE细胞变化及相互作用，我们使用了免疫细胞化学技术以及针对细胞角蛋白（CK）和胶质纤维酸性蛋白（GFAP）的抗体。在营养不良视网膜中Müller细胞突起增殖之前，RPE细胞中的CK丝形成了一个周向网络，胞质和核周标记强烈，这与对照RPE细胞相同。在Müller细胞突起进入膜碎片区并形成RPE-Müller细胞接触后，RPE细胞变得多形，并在碎片区伸出突出的顶端突起。一些CK反应性RPE细胞从Bruch膜脱离并迁移到碎片区。电子显微镜研究显示此时RPE-Müller细胞有广泛的紧密接触区域。未观察到质膜明显的连接特化，但突出的管泡状结构占据了改变的RPE和Müller细胞突起的细胞质。在RPE血管化之后，肥大的CK阳性细胞围绕血管并伴随它们进入内视网膜。电子显微镜分析表明，与RPE相关的血管有窗孔且没有血管周围的神经胶质鞘。观察到RPE细胞明显增殖以及CK丝重新分布。我们的研究表明，RPE细胞改变伴随着Müller细胞和血管变化，这导致营养不良大鼠视网膜中RPE-Müller细胞和RPE-内皮细胞关系发生改变。RPE、Müller和内皮细胞之间改变的关系可能导致细胞间相互作用增加，并促进患病视网膜中所有三种细胞类型的增殖和转变。
