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视网膜前膜中血小板源性生长因子及其受体的异构体:在视网膜色素上皮细胞中的免疫定位

Isoforms of platelet-derived growth factor and its receptors in epiretinal membranes: immunolocalization to retinal pigmented epithelial cells.

作者信息

Vinores S A, Henderer J D, Mahlow J, Chiu C, Derevjanik N L, Larochelle W, Csaky C, Campochiaro P A

机构信息

Wilmer Ophthalmological Institute, Johns Hopkins University, School of Medicine, Baltimore, MD 21287, USA.

出版信息

Exp Eye Res. 1995 Jun;60(6):607-19. doi: 10.1016/s0014-4835(05)80003-x.

Abstract

Epiretinal membranes (ERMs) form on the inner surface of the retina in conjunction with various ocular disease processes, but the factors controlling their development are not understood. The predominant cell types involved are retinal pigmented epithelial (RPE) cells and retinal glia. Cultured RPE cells secrete platelet-derived growth factor (PDGF), which is chemotactic and mitogenic for both RPE cells and retinal glia and, therefore, could be involved in the development of ERMs. In the present study, we performed immunohistochemical staining for PDGF A chain (PDGF-A), PDGF B chain (PDGF-B), and both types of PDGF receptors (PDGFr alpha and PDGFr beta) on ERMs associated with various disease processes. PDGF-A is detected in most ERMs, regardless of the associated disease process, and it appears to be localized predominantly in RPE cells, recognized by the presence of pigment and the immunohistochemical demonstration of some or all of the following RPE-associated epitopes: class III beta-tubulin, keratin, the 65-kDa microsomal protein recognized by the RPE9 antibody, and cellular retinaldehyde-binding protein. PDGF-B is found only in minor subpopulations of cells in about half of the ERMs evaluated and, with only occasional exceptions, appears to be localized almost entirely in blood-borne cells found in and around vessels in vascularized ERMs. Both PDGFr alpha and PDGFr beta are demonstrated in most ERMs with neither isotype consistently predominating: they are found predominantly on RPE cells with many cells expressing both receptor types. ERMs with little or no RPE cell component contain little or no PDGF and PDGF receptor, whereas those in which the RPE cell represents the major cell type, have widespread PDGF and PDGF receptor positivity. These findings show that RPE cells in ERMs produce PDGF-A and PDGF alpha and PDGF beta receptors and suggest that autocrine and paracrine stimulation with PDGF may be involved in ERM pathogenesis.

摘要

视网膜前膜(ERM)与多种眼部疾病过程相关,在视网膜内表面形成,但其发育的控制因素尚不清楚。主要涉及的细胞类型是视网膜色素上皮(RPE)细胞和视网膜神经胶质细胞。培养的RPE细胞分泌血小板衍生生长因子(PDGF),它对RPE细胞和视网膜神经胶质细胞具有趋化性和促有丝分裂作用,因此可能参与ERM的发育。在本研究中,我们对与各种疾病过程相关的ERM进行了PDGF A链(PDGF-A)、PDGF B链(PDGF-B)以及两种类型的PDGF受体(PDGFrα和PDGFrβ)的免疫组织化学染色。无论相关疾病过程如何,大多数ERM中都能检测到PDGF-A,它似乎主要定位于RPE细胞,可通过色素的存在以及以下部分或全部与RPE相关的表位的免疫组织化学证明来识别:III类β-微管蛋白、角蛋白被RPE9抗体识别的65 kDa微粒体蛋白以及细胞视黄醛结合蛋白。在大约一半评估的ERM中,仅在少数细胞亚群中发现PDGF-B,并且除偶尔例外,它似乎几乎完全定位于血管化ERM中血管内和周围的血源性细胞中。大多数ERM中都显示出PDGFrα和PDGFrβ,两种同型均无一致的优势:它们主要存在于RPE细胞上,许多细胞同时表达两种受体类型。几乎没有或没有RPE细胞成分的ERM含有很少或没有PDGF和PDGF受体,而RPE细胞是主要细胞类型的ERM则具有广泛的PDGF和PDGF受体阳性。这些发现表明ERM中的RPE细胞产生PDGF-A以及PDGFα和PDGFβ受体,并提示PDGF的自分泌和旁分泌刺激可能参与ERM的发病机制。

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