MULLER CELL CHANGES PRECEDE PHOTORECEPTOR CELL DEGENERATION IN THE AGE-RELATED RETINAL DEGENERATION OF THE FISCHER-344 RAT
MULLER CELL CHANGES PRECEDE PHOTORECEPTOR CELL DEGENERATION IN THE AGE-RELATED RETINAL DEGENERATION OF THE FISCHER-344 RAT
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DOI：
10.1016/0006-8993(95)00647-9
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发表时间：
1995-11-06
期刊：
影响因子：
2.9
通讯作者：
DELCERRO, M
中科院分区：
文献类型：
--
作者：
DILORETO, DA;MARTZEN, MR;DELCERRO, M
以前，我们已经使用描述性病理学和组织形态学，以及功能测试，以表征年龄相关的视网膜变性的Fischer 344大鼠。这些研究表明，在这一过程中米勒细胞和感光细胞之间的关联。本研究的目的是进一步研究这些细胞类型在视网膜变性的发展和进展中各自的作用。首先通过光学显微镜和电子显微镜研究了3-24个月大的雄性Fischer 344大鼠的视网膜。由于Muller细胞在病理状态下大量表达GFAP，因此通过免疫细胞化学和一维和二维凝胶电泳后的免疫印迹研究GFAP含量。显微镜下，在12个月，穆勒细胞显示梯度的GFAP的免疫反应性是最小的中央视网膜，积极的径向进程中的赤道，并在周边大量表达。在这个年龄段，感光细胞在远外围刚刚开始退化，而在赤道和中心区域则显得健康。到24个月时，在感光细胞变性最严重的外周区域观察到穆勒细胞肥大，而穆勒细胞突起的免疫反应性在感光细胞变性之前进一步向中心区域扩散。因此，Muller细胞的变化实际上在时间和位置上先于感光细胞变性。通过在一维和二维PAGE后测量GFAP证实了这种现象。这些发现表明，Muller细胞的变化先于慢性感光细胞变性的老化Fischer 344大鼠，并与假设，即Muller细胞的改变可能是这种年龄相关的视网膜变性的主要机制是一致的。
Previously, we have used descriptive pathology and histomorphometry, as well as functional testing to characterize the age-related retinal degeneration in the Fischer 344 rat. These studies suggested an association between Muller cells and photoreceptor cells in this process. The purpose of the present study was to further investigate the respective roles of these cell types in the development and progression of the retinal degeneration. Retinas from male Fischer 344 rats aged 3-24 months were first studied by light and electron microscopy. Since Muller cells abundantly express GFAP during pathological states, GFAP content was studied by immunocytochemistry and by immunoblotting following one- and two-dimensional gel electrophoresis. Microscopically, at 12 months, Muller cells showed a gradient of immunoreactivity for GFAP that was minimal in the central retina, positive for their radial processes in the equator, and abundantly expressed in the periphery. At this age, the photoreceptor cells were just beginning to degenerate in the far periphery, while they appeared healthy in the equatorial and central regions. By 24 months, Muller cell hypertrophy was seen in the peripheral regions where photoreceptor cell degeneration was most severe, while the immunoreactivity of the Muller cell processes spread further toward the central regions, ahead of the degeneration of the photoreceptor cells. Thus, Muller cell changes actually preceded photoreceptor degeneration in time and location. This phenomenon was confirmed by measurement of GFAP after one- and two-dimensional PAGE. These findings show that Muller cell changes precede chronic photoreceptor cell degeneration in the aging Fischer 344 rat and are consistent with the hypothesis that Muller cell alteration may be the primary mechanism of this age-related retinal degeneration.