Amin R H, Frank R N, Kennedy A, Eliott D, Puklin J E, Abrams G W
Kresge Eye Institute, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Invest Ophthalmol Vis Sci. 1997 Jan;38(1):36-47.
To determine whether vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which have been implicated in the development of retinal and choroidal neovascularization, are present in the retinas and optic nerves of patients with diabetes before proliferative retinopathy appears.
Light microscopic immunocytochemistry using antibodies to VEGF, bFGF, vimentin, glial fibrillary acidic protein (GFAP), and factor VIII on frozen sections from eyes of patients with diabetes without proliferative retinopathy, eyes of patients without diabetes and without known ocular disease, and eyes with disciform age-related macular degeneration (ARMD). Retinal vascular digest preparations to evaluate microvascular abnormalities.
Based on morphology and on GFAP and vimentin immunopositivity, retinas from all subjects with diabetes immunostained strongly to VEGF in elongated processes that appeared to be Müller cells. Glial cells within septa surrounding axons in the anterior optic nerve also immunostained for VEGF, as did endothelial cells of some posterior retinal blood vessels and some retinal pigment epithelial cells. Retinas from eyes with disciform ARMD immunostained for VEGF, though less extensively than did those of subjects with diabetes. Retinas and optic nerves from subjects without ocular disease were VEGF negative. Basic fibroblast growth factor was expressed minimally in the inner retinal layers of subjects with and without diabetes, but it was substantial in the photoreceptor layer of all eyes. Vascular endothelial growth factor immunopositivity was present in eyes with no, or little, retinal vascular anatomic abnormality in digest preparations.
Vascular endothelial growth factor expression precedes retinal neovascularization in the retinas and the optic nerves of humans with diabetes. Its localization to glial cells of the inner retina and the anterior optic nerve suggests a relationship to neovascularization in these sites. That VEGF immunopositivity may occur when there is no anatomic evidence of retinal nonperfusion and little likelihood of retinal neovascularization suggests the possibility that ischemia may not be the sole stimulus for VEGF expression.
确定在增生性视网膜病变出现之前，糖尿病患者的视网膜和视神经中是否存在与视网膜和脉络膜新生血管形成有关的血管内皮生长因子（VEGF）和碱性成纤维细胞生长因子（bFGF）。
对无增生性视网膜病变的糖尿病患者、无糖尿病且无已知眼部疾病的患者以及患有盘状年龄相关性黄斑变性（ARMD）的患者的眼组织冰冻切片，使用抗VEGF、bFGF、波形蛋白、胶质纤维酸性蛋白（GFAP）和因子VIII的抗体进行光镜免疫细胞化学检测。制备视网膜血管消化标本以评估微血管异常情况。
基于形态学以及GFAP和波形蛋白免疫阳性结果，所有糖尿病患者的视网膜在似乎是Müller细胞的细长突起中对VEGF呈强免疫染色。视神经前部轴突周围间隔内的胶质细胞也对VEGF呈免疫染色，一些视网膜后血管的内皮细胞和一些视网膜色素上皮细胞也如此。患有盘状ARMD的患者的视网膜对VEGF呈免疫染色，但其范围不如糖尿病患者的视网膜广泛。无眼部疾病的患者的视网膜和视神经VEGF呈阴性。碱性成纤维细胞生长因子在有糖尿病和无糖尿病患者的视网膜内层中表达极少，但在所有眼睛的光感受器层中表达丰富。在消化标本中，视网膜血管解剖结构无异常或仅有轻微异常的眼中也存在VEGF免疫阳性。
血管内皮生长因子在糖尿病患者的视网膜和视神经中的表达先于视网膜新生血管形成。其在内层视网膜和视神经前部的胶质细胞中的定位表明与这些部位的新生血管形成有关。当没有视网膜无灌注的解剖学证据且视网膜新生血管形成的可能性很小时仍出现VEGF免疫阳性，这提示缺血可能不是VEGF表达的唯一刺激因素。
