胶质纤维酸性蛋白（GFAP）在早期与晚期年龄相关性黄斑变性中的差异表达：一项定量分析
Differential expression of GFAP in early v late AMD: a quantitative analysis.
作者信息
Wu K H C, Madigan M C, Billson F A, Penfold P L
机构信息
Department of Clinical Ophthalmology, Save Sight Institute, University of Sydney, Sydney NSW 2006, Australia.
出版信息
Br J Ophthalmol. 2003 Sep;87(9):1159-66. doi: 10.1136/bjo.87.9.1159.
BACKGROUND/AIMS: Glial fibrillary acidic protein (GFAP) is an established indicator of retinal stress; its expression in retinal astrocytes and Müller cells has been demonstrated to be modulated by cytokines and retinal pathology, including age related macular degeneration (AMD). This study aims to quantify the modulation of GFAP expression in retinas with drusen and atrophic AMD versus normal age matched controls.
METHODS
Following a histopathological survey, 17 donor retinas were classified into four groups: drusen (n=5), geographic atrophy (GA) (n=6), aged normal (n=3), and young normal (n=3). Paramacular cryosections were immunolabelled with GFAP antibody, examined by confocal microscopy, and quantified by NIH digital image analysis. Groups were matched for potential confounding factors including age, sex, and postmortem delay.
RESULTS
A significant increase in GFAP immunolabelling of macroglia was noted in aged normal compared with young normal retinas (p<0.04). Upregulation of GFAP immunoreactivity involving astrocytes was observed in drusen retinas compared with control retinas (p<0.03). GFAP was also upregulated in retinas with GA compared with controls (p<0.05) and in retinas with GA compared with drusen (p<0.04), both involving Müller cells. Discrete regions of GFAP upregulation in Müller cells were associated with drusen formation. In GA specimens atrophied retinal pigment epithelium (RPE) was substituted by GFAP immunoreactive Müller cell processes (gliosis).
CONCLUSION
This study provides a quantitative assessment of GFAP modulation in ageing and AMD affected retinas. Morphological observations were consistent with quantitative analyses indicating differential modulation of GFAP immunoreactivity in inner and outer retina. Upmodulation of GFAP in inner retina and astroglial processes was predominantly associated with drusen, while in outer retina Müller glia upmodulation of GFAP was associated with disruption of the RPE and blood-retinal barrier.
背景/目的：胶质纤维酸性蛋白（GFAP）是视网膜应激的既定指标；其在视网膜星形胶质细胞和Müller细胞中的表达已被证明受细胞因子和视网膜病变（包括年龄相关性黄斑变性（AMD））的调节。本研究旨在量化有玻璃膜疣和萎缩性AMD的视网膜与年龄匹配的正常对照相比GFAP表达的调节情况。
方法
经过组织病理学检查，17个供体视网膜被分为四组：玻璃膜疣（n = 5）、地图样萎缩（GA）（n = 6）、老年正常（n = 3）和年轻正常（n = 3）。黄斑旁冰冻切片用GFAP抗体进行免疫标记，通过共聚焦显微镜检查，并通过美国国立卫生研究院数字图像分析进行量化。对各组潜在的混杂因素（包括年龄、性别和死后延迟时间）进行匹配。
结果
与年轻正常视网膜相比，老年正常视网膜中神经胶质细胞的GFAP免疫标记显著增加（p < 0.04）。与对照视网膜相比，玻璃膜疣视网膜中涉及星形胶质细胞的GFAP免疫反应性上调（p < 0.03）。与对照相比，GA视网膜中的GFAP也上调（p < 0.05），与玻璃膜疣视网膜相比，GA视网膜中的GFAP也上调（p < 0.04），两者均涉及Müller细胞。Müller细胞中GFAP上调的离散区域与玻璃膜疣形成有关。在GA标本中，萎缩的视网膜色素上皮（RPE）被GFAP免疫反应性Müller细胞突起（胶质增生）所取代。
结论
本研究对衰老和AMD影响的视网膜中GFAP的调节进行了定量评估。形态学观察结果与定量分析一致，表明视网膜内外层GFAP免疫反应性存在差异调节。视网膜内层和星形胶质细胞突起中GFAP的上调主要与玻璃膜疣有关，而视网膜外层Müller胶质细胞中GFAP的上调与RPE和血视网膜屏障的破坏有关。
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