Drusen-associated degeneration in the retina
Drusen-associated degeneration in the retina
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DOI：
10.1167/iovs.03-0436
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发表时间：
2003-10-01
影响因子：
4.4
通讯作者：
Johnson, LV
中科院分区：
文献类型：
--
作者：
Johnson, PT;Lewis, GP;Johnson, LV
目的.玻璃疣是在视网膜色素上皮（RPE）和布鲁赫膜之间形成的大小不一的细胞外沉积物。它们常见于老年眼睛，然而，许多和/或融合性玻璃疣是年龄相关性黄斑变性的重要风险因素。本研究的目的是调查玻璃疣对视网膜上覆细胞的影响。从人供体眼睛解剖含有视网膜和RPE/脉络膜的组织，包埋在琼脂糖中，并使用振动切片机在100 μ m处切片。用一组标记神经胶质细胞、第一、第二和第三级视网膜神经元的抗体对切片进行免疫染色，并进行共聚焦显微镜检查。视网膜细胞，覆盖在软和硬玻璃疣表现出许多结构和分子异常。通常仅在视杆光感受器的外节中可检测到，视杆视蛋白免疫标记也在覆盖玻璃疣的光感受器的内节、细胞体、轴突和轴突末端中观察到。用这种抗体标记还揭示了杆内节和外节的偏转和缩短。视锥光感受器表现出类似的结构异常，以及减少视锥蛋白免疫反应。还观察到感光细胞突触末梢中的Drusen相关异常。此外，中间丝蛋白免疫反应性（波形蛋白和神经胶质细胞酸性蛋白）的增加，观察到在穆勒神经胶质细胞的视网膜覆盖玻璃疣的地区。软玻璃疣和硬玻璃疣在黄斑区和黄斑外区均与类似的效应谱相关。二级和三级神经元，包括双极、水平、无长突和神经节细胞都未受影响。在光感受器和Muller神经胶质细胞中观察到的结构和分子异常仅限于直接覆盖和紧邻玻璃疣的视网膜区域;更远的视网膜区域似乎未受干扰。值得注意的是，在小的亚临床玻璃疣上观察到显著的异常。视网膜细胞覆盖软玻璃疣和硬玻璃疣表现出结构和分子异常，表明感光细胞变性和Muller神经胶质激活。这些异常类似于许多形式的视网膜变性常见的变性效应，但仅限于直接覆盖玻璃疣的区域。这表明，感光细胞的功能受到损害的结果，玻璃疣的形成。
PURPOSE. Drusen are variably sized extracellular deposits that form between the retinal pigmented epithelium (RPE) and Bruch's membrane. They are commonly found in aged eyes, however, numerous and/or confluent drusen are a significant risk factor for age-related macular degeneration. The purpose of this study was to investigate the impact of drusen on overlying cells of the retina.METHODS. Tissue containing retina and RPE/choroid was dissected from human donor eyes, embedded in agarose, and sectioned at 100 mum using a vibratome. Sections were immunostained with a panel of antibodies that labeled glial cells, first-, second-, and third-order retinal neurons and processed for confocal microscopy.RESULTS. Retinal cells that overlie both soft and hard drusen exhibited numerous structural and molecular abnormalities. Normally detectable only in the outer segments of rod photoreceptors, rod opsin immunolabeling was also observed in the inner segment, cell body, axon, and axon terminal of photoreceptors that overlie drusen. Labeling with this antibody also revealed the deflection and shortening of rod inner and outer segments. Cone photoreceptors displayed similar structural abnormalities, as well as a decrease in cone opsin immunoreactivity. Drusen-associated abnormalities in the synaptic terminals of photoreceptor cells were also observed. In addition, an increase in intermediate filament protein immunoreactivity (vimentin and glial fibrillary acidic protein) was observed within Muller glial cells in areas of retina overlying drusen. Both soft and hard drusen were associated with a similar spectrum of effects in both macular and extramacular regions. Second- and third-order neurons, including bipolar, horizontal, amacrine, and ganglion cells all appeared unaffected. The structural and molecular abnormalities observed in photoreceptors and Muller glial cells were confined to retinal regions directly overlying and immediately adjacent to drusen; more distant retinal regions appeared unperturbed. Remarkably, significant abnormalities were observed over small subclinical drusen.CONCLUSIONS. Retinal cells overlying both soft and hard drusen exhibit structural and molecular abnormalities indicative of photoreceptor degeneration and Muller glial activation. These abnormalities resemble the degenerative effects common to many forms of retinal degeneration, but are confined to areas directly overlying drusen. This suggests that photoreceptor cell function is compromised as a consequence of drusen formation.