Impairment of Intrinsically Photosensitive Retinal Ganglion Cells Associated With Late Stages of Retinal Degeneration
Impairment of Intrinsically Photosensitive Retinal Ganglion Cells Associated With Late Stages of Retinal Degeneration
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DOI：
10.1167/iovs.13-12120
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发表时间：
2013-07-01
影响因子：
4.4
通讯作者：
Cuenca, Nicolas
中科院分区：
文献类型：
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作者：
Esquiva, Gema;Lax, Pedro;Cuenca, Nicolas
目的.为了评价转基因P23 H大鼠视网膜神经节细胞（ipRGC）中含有黑视素的内在光敏性细胞的定量和定性年龄相关变化，对常染色体显性遗传视网膜色素变性（RP）动物模型进行了检查。在从4、12和18月龄的P23 H和Sprague-Dawley（SD）大鼠提取的视网膜中通过免疫组织化学表征ipRGC密度、形态和完整性。SD和P23 H大鼠在整个实验阶段之间的差异，以及它们之间的相互作用，进行了形态学评价。在大鼠视网膜中，我们已经鉴定出具有树突的ipRGC，所述树突在内部丛状层的外缘（M1）或内侧（M2）中分层，并且在外部和内部丛（M3）中分层。一小群M1细胞的胞体位于内核层（M1 d）。在SD大鼠中，ipRGC在平均细胞密度或分析的形态学参数方面均未显示出与年龄相关的显著变化。然而，P23 H大鼠中ipRGC的平均密度在4至18月龄之间下降了约67%。此外，这些动物中的ipRGC在树突面积、每个细胞的分支点和末端神经突尖端的数量以及Sholl面积方面表现出进行性的年龄依赖性减少。在视网膜色素变性的P23 H大鼠模型中，含黑视蛋白的神经节细胞的密度、整体性和树突状分支在退行性疾病的晚期阶段减少。
PURPOSE. To evaluate quantitative and qualitative age-related changes in intrinsically photosensitive melanopsin-containing retinal ganglion cells (ipRGCs) in transgenic P23H rats, an animal model of autosomal dominant retinitis pigmentosa (RP) was examined.METHODS. ipRGC density, morphology, and integrity were characterized by immunohistochemistry in retinas extracted from P23H and Sprague-Dawley (SD) rats aged 4, 12, and 18 months. Differences between SD and P23H rats throughout the experimental stages, as well as the interactions among them, were morphologically evaluated.RESULTS. In rat retinas, we have identified ipRGCs with dendrites stratifying in either the outer margin (M1) or inner side (M2) of the inner plexiform layer, and in both the outer and inner plexuses (M3). A small group of M1 cells had their somas located in the inner nuclear layer (M1d). In SD rats, ipRGCs showed no significant changes associated with age, in terms of either mean cell density or the morphologic parameters analyzed. However, the mean density of ipRGCs in P23H rats fell by approximately 67% between 4 and 18 months of age. Moreover, ipRGCs in these animals showed a progressive age-dependent decrease in the dendritic area, the number of branch points and terminal neurite tips per cell, and the Sholl area.CONCLUSIONS. In the P23H rat model of retinitis pigmentosa, density, wholeness, and dendritic arborization of melanopsin-containing ganglion cells decrease in advanced stages of the degenerative disease.