Role of Muller cells in cone mosaic rearrangement in a rat model of retinitis pigmentosa.
Role of Muller cells in cone mosaic rearrangement in a rat model of retinitis pigmentosa.
复制标题
Muller 细胞在视网膜色素变性大鼠模型中锥体镶嵌重排中的作用。
DOI：
10.1002/glia.21183
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发表时间：
2011
期刊：
影响因子：
6.2
通讯作者：
Grzywacz,NorbertoM
中科院分区：
文献类型：
--
作者：
Lee,Eun-Jin;Ji,Yerina;Zhu,ColleenL;Grzywacz,NorbertoM
视网膜色素变性（Retinitis Pigmentosa，RP）是一种可导致失明的遗传性视网膜变性疾病。这种疾病的主要病理事件是由于基因突变导致的杆细胞死亡。S334 ter ‐line‐3大鼠是一种转基因模型，用于表达与RP中发现的类似的视紫红质突变。在这项研究中，视杆细胞的死亡引发了锥状镶嵌体的重组，形成了一系列有序的环。有四点意见与理解这种重组有关。首先，杆在热点中死亡，热点以圆形波的形式逐渐增加，留下无杆区。第二，在这些区域周围形成锥形环。第三，重塑的Müller神经胶质突起包裹视锥细胞并填充其环的中心。在环中显示位于感光细胞内节和Müller细胞顶端突起之间的闭锁小带-1。第四，这些环在视锥细胞死亡开始之前形成，并一直维持到RP晚期。根据这些观察结果，我们假设视锥细胞相互作用介导并维持环。可以通过注射DL-α-氨基己二酸（AAA）进行该假设的检验，已知其会破坏Müller细胞代谢。在P50单次玻璃体内注射AAA在注射后3天破坏视锥环。这些结果表明，锥体细胞在环中的重排是由米勒细胞在RP调制。因此，如果光感受器和缪勒神经胶质之间的关系得到更好的理解，后者可能被操纵有效的神经保护或恢复正常的锥阵列。© 2011 Wiley‐利斯公司
Retinitis pigmentosa (RP) is a type of inherited retinal degenerative disease, which leads to blindness. The primary pathological event of this disease is the death of rods because of genetic mutations. The S334ter‐line‐3 rat is a transgenic model developed to express a rhodopsin mutation similar to that found in RP. In this study, the rod's death triggered a reorganization of the cone mosaic into an orderly array of rings. Four observations were relevant to understand this reorganization. First, rods died in hot spots, which progressively increased as circular waves, leaving rod‐less zones behind. Second, rings of cones formed around these zones. Third, remodeled Müller glia processes enveloped cones and filled the center of their rings. Zonula occludens‐1 located between the photoreceptor inner segments and the apical processes of Müller cells showed in the rings. Fourth, these rings were formed before the onset of cone cell deaths and were maintained until late stages of RP. From these observations, we hypothesize that cone‐Müller‐cell interactions mediate and maintain the rings. A test of this hypothesis can be performed by injecting DL‐α‐aminoadipic acid (AAA), which is known to disrupt Müller cell metabolism. A single intravitreal injection of AAA at P50 disrupted the rings of cones 3 days after the injection. These findings indicate that the rearrangement of cones in rings is modulated by Müller cells in RP. Thus, if the relationship between photoreceptors and Müller glia is better understood, the latter could potentially be manipulated for effective neuroprotection or the restoration of normal cone arrays. © 2011 Wiley‐Liss, Inc.