Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa.
Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa.
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DOI：
10.3389/fncel.2015.00484
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发表时间：
2015
影响因子：
5.3
通讯作者：
Cuenca N
中科院分区：
文献类型：
--
作者：
Fernández-Sánchez L;Lax P;Campello L;Pinilla I;Cuenca N
目的：色素性视网膜炎包括一组影响光感受器结构和功能的进行性视网膜退行性疾病。其次是光感受器的丧失，视网膜血管化减少，这似乎影响细胞退化过程。视网膜大胶质细胞、星形胶质细胞和穆勒细胞为视网膜神经元提供支持，是维持正常视网膜功能的基础。本研究的目的是研究 P23H 大鼠视网膜变性期间大胶质细胞变化的演变。方法：采用P18～18月龄纯合子P23H line-3大鼠研究疾病的演变过程，并以SD大鼠作为对照。使用针对 GFAP、波形蛋白和转导蛋白的抗体进行免疫标记，以可视化大胶质细胞和视锥细胞。结果：在 P23H 大鼠中，观察到 Müller 细胞中 GFAP 标记的增加是视网膜神经胶质增生的早期指标。在 4 个月和 12 个月大时，P23H 大鼠的 Müller 细胞顶端突起聚集成烟花状结构，与外核层中锥体变性的环形区域相关。 16 个月大时未观察到这些结构。 4 月龄和 12 月龄时，P23H 大鼠的星形胶质细胞数量高于 SD 匹配对照，支持星形胶质细胞增殖的观点。随着疾病的进展，星形胶质细胞表现出形态恶化和明显肥大。星形细胞过程复杂性的增加与 P23H 与 SD 大鼠视网膜神经节细胞层 (GCL) 内连接蛋白 43 表达的增加和连接蛋白 43 免疫反应性点的密度较高相关。结论：在 P23H 大鼠视网膜色素变性模型中，光感受器的丧失引发了影响视网膜内部的神经胶质细胞数量和形态的重大变化。
Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina.