Famiglietti Edward V, Stopa Edward G, McGookin Edward D, Song Philip, LeBlanc Victoria, Streeten Barbara W
Department of Pathology, Division of Neuropathology, Brown University School of Medicine, Rhode Island Hospital, APC-12, 593 Eddy Street, Providence, RI 02903, USA.
Brain Res. 2003 Apr 18;969(1-2):195-204. doi: 10.1016/s0006-8993(02)03766-6.
In order to establish the cellular and subcellular localization of the chemokine protein, vascular endothelial growth factor (VEGF) or vascular permeability factor, in adult human retina, we employed immunocytochemistry with double immunolabeling, using a primary antibody to amino acids 1-10 of VEGF, together with antibodies to vimentin (intermediate filaments, labeling Müller cells) or to neuron-specific enolase (labeling retinal neurons). In adult human retina, VEGF-like immunoreactivity (VEGF-IR) is found in Müller cell processes, where typically it is found in the cytoplasm in close association with Vimentin-labeled (VM-IR) intermediate filaments. VEGF-IR is sometimes found diffusely in Müller cell bodies and nuclei. VEGF-IR is found in all major classes of retinal neurons, as demonstrated by co-localization with neuron-specific enolase (NSE)-IR, but is especially prominent in cell bodies of amacrine cells (ACs) (including displaced ACs) and ganglion cells (GCs). Generally, VEGF-IR is more prominent in the nucleus, while NSE-IR is more prominent in the cytoplasm and neurites. In blood vessels, VEGF-IR co-localizes with VM-IR, marking blood vessel endothelial cells, whereas NSE-IR apparently marks the layer of smooth muscle cells. These cellular findings regarding the retinal localization of VEGF-IR are consistent with VEGF synthesis in and its export from retinal neurons, particularly amacrine and ganglion cells, as well as in glia, specifically Müller cells, and suggest that retinal neurons normally provide continuous trophic support for their retinal blood supply.
为了确定趋化因子蛋白、血管内皮生长因子(VEGF)或血管通透因子在成人视网膜中的细胞及亚细胞定位,我们采用了双重免疫标记的免疫细胞化学方法,使用针对VEGF第1至10个氨基酸的一抗,同时结合波形蛋白抗体(中间丝,标记Müller细胞)或神经元特异性烯醇化酶抗体(标记视网膜神经元)。在成人视网膜中,VEGF样免疫反应性(VEGF-IR)见于Müller细胞突起,通常在细胞质中与波形蛋白标记的(VM-IR)中间丝紧密相连。VEGF-IR有时也散见于Müller细胞体和细胞核中。通过与神经元特异性烯醇化酶(NSE)-IR共定位证明,VEGF-IR存在于所有主要类型的视网膜神经元中,但在无长突细胞(ACs)(包括移位的ACs)和神经节细胞(GCs)的细胞体中尤为明显。一般来说,VEGF-IR在细胞核中更明显,而NSE-IR在细胞质和神经突中更明显。在血管中,VEGF-IR与VM-IR共定位,标记血管内皮细胞,而NSE-IR显然标记平滑肌细胞层。这些关于VEGF-IR在视网膜中定位的细胞研究结果与VEGF在视网膜神经元,特别是无长突细胞和神经节细胞以及神经胶质细胞(特别是Müller细胞)中的合成及其输出一致,并表明视网膜神经元通常为其视网膜血液供应提供持续的营养支持。