Survival and remodeling of melanopsin cells during retinal dystrophy
Survival and remodeling of melanopsin cells during retinal dystrophy
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DOI：
10.1017/s0952523808080309
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发表时间：
2008-03-01
影响因子：
1.9
通讯作者：
Jeffery, Glen
中科院分区：
文献类型：
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作者：
Vugler, Anthony A.;Semo, Maayan;Jeffery, Glen
内视网膜的黑视蛋白阳性、本质上感光的视网膜神经节细胞（ipRGC）已被证明可以向整个大脑发送广泛的投射。为了研究这种重要细胞类型在视网膜营养不良期间的反应，我们使用皇家外科学院 (RCS) 营养不良大鼠，这是视网膜变性的主要模型。我们发现 ipRGC 表现出独特的分子特征，该特征在外视网膜病理学的早期阶段（15 周龄）保持不变。特别是，这些细胞表达 β III 微管蛋白、α-乙酰化微管蛋白和微管相关蛋白 (MAP)，同时对其他 RGC 标记物（如神经丝、钙视网膜蛋白和小清蛋白）保持阴性。到 14 个月大时，黑视蛋白阳性纤维侵入营养不良性视网膜的异位位置，ipRGC 轴突/树突变得扭曲（这一过程可能涉及血管重塑）。黑视蛋白过程的形态异常与 MAP1b 免疫反应性升高和 α-乙酰化微管蛋白减少有关。整个 ipRGC 的定量显示，随着年龄的增长，黑视蛋白细胞数量减少。着眼于视网膜周边，我们发现黑视蛋白细胞密度显着下降，而黑视蛋白阳性过程的稳定性则相反。除了这些发现之外，我们还首次描述了远周视网膜中独特的黑视蛋白丛，该结构与短波长视蛋白锥体丰富的边缘一致。我们得出的结论是，随着疾病的进展，RCS 营养不良大鼠中一些 ipRGC 会丢失，并且这种丢失可能涉及血管重塑。然而，大量黑视蛋白阳性细胞存活到视网膜变性的晚期，并显示出响应病理学重塑的迹象。我们的研究结果强调了早期干预人类视网膜疾病以保持视网膜内部感光网络完整性的重要性。
The melanopsin positive, intrinsically photosensitive retinal ganglion cells (ipRGCs) of the inner retina have been shown to send wide-ranging projections throughout the brain. To investigate the response of this important cell type during retinal dystrophy, we use the Royal College of Surgeons (RCS) dystrophic rat, a major model of retinal degeneration. We find that ipRGCs exhibit a distinctive molecular profile that remains unaltered during early stages of outer retinal pathology (15 weeks of age). In particular, these cells express beta III tubulin, a-acetylated tubulin, and microtubule-associated proteins (MAPs), while remaining negative for other RGC marker's such as neurofilaments, calretinin, and parvalbumin. By 14 months of age, melanopsin positive fibers invade ectopic locations in the dystrophic retina and ipRGC axons/dendrites become distorted (a process that may involve vascular remodeling). The morphological abnormalities in melanopsin processes are associated with elevated immunoreactivity for MAP1b and a reduction in a-acetylated tubulin. Quantification of ipRGCs in whole mounts reveals reduced melanopsin cell number with increasing age. Focusing on the retinal periphery, we find a significant decline in melanopsin cell density contrasted by a stability of melanopsin positive processes. In addition to these findings, we describe for the first time, a distinct plexus of melanopsin processes in the far peripheral retina, a structure that is coincident with a short wavelength opsin cone-enriched rim. We conclude that some ipRGCs are lost in RCS dystrophic rats as the disease progresses and that this loss may involve vascular remodeling. However, a significant number of melanopsin positive cells survive into advanced stages of retinal degeneration and show indications of remodeling in response to pathology. Our findings underline the importance of early intervention in human retinal disease in order to preserve integrity of the inner retinal photoreceptive network.