Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited photoreceptor degeneration.
Retinal ganglion cells survive and maintain normal dendritic morphology in a mouse model of inherited photoreceptor degeneration.
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DOI：
10.1523/jneurosci.4968-08.2008
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发表时间：
2008-12-24
期刊：
影响因子：
--
通讯作者：
Strettoi E
中科院分区：
文献类型：
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作者：
Mazzoni F;Novelli E;Strettoi E
色素性视网膜炎（RP）是一种以进行性光感受器死亡为特征的遗传性疾病家族，是致盲的主要原因，目前尚无有效的治疗方法。尽管这种疾病的遗传异质性，最近的动物模型数据表明，光感受器的退化触发其突触后伴侣之间的定型重塑。特别是，双极和水平细胞可能经历树突状萎缩和继发性死亡。本研究的目的是调查是否伴随的变化也发生在神经节细胞（RGC），唯一的视网膜投射神经元的大脑和各种治疗方法RP的建议基板。我们评估了保留的形态，整体架构和生存的RGC在小鼠模型的RP在不同阶段的疾病。为了研究单个RGCs的形态，我们通过杂交Thy 1-GFP-M小鼠和rd 10突变体产生了一个新的小鼠系，Thy 1-GFP-M小鼠在少量的异质性RGCs类型中表达GFP，rd 10突变体是一种常染色体隐性遗传RP模型，表现出典型的视杆-视锥变性。我们发现，在生命的3至9个月的时间跨度内，RGC结构、存活和向更高视觉中心的投射都得到了显着的保护，远远超过了光感受器的死亡。因此，与二级神经元不同，RGCs表现为相当稳定的细胞群体，可能构成通过电子假体或直接表达光敏蛋白来恢复RP个体视力的有利基质。
Retinitis Pigmentosa (RP), a family of inherited disorders characterized by progressive photoreceptor death, is a leading cause of blindness with no available cure. Despite the genetic heterogeneity underlying the disease, recent data on animal models show that the degeneration of photoreceptors triggers stereotyped remodeling among their postsynaptic partners. In particular, bipolar and horizontal cells might undergo dendritic atrophy and secondary death. The aim of this study was to investigate whether or not concomitant changes also occur in ganglion cells (RGCs), the only retinal projection neurons to the brain and the proposed substrate for various therapeutic approaches for RP. We assessed the retention of morphology, overall architecture and survival of RGCs in a mouse model of RP at various stages of the disease. To study the morphology of single RGCs , we generated a new mouse line by crossing Thy1-GFP-M mice, which express GFP in a small number of heterogeneous RGCs types, and rd10 mutants, a model of autosomal recessive RP, which exhibit a typical rod-cone degeneration. We show remarkable preservation of RGC structure, survival and projections to higher visual centers in the time span from 3 to 9 months of life, well beyond the death of photoreceptors. Thus, unlike second order neurons, RGCs appear as a considerably stable population of cells, potentially constituting a favorable substrate for restoring vision in RP individuals by means of electronic prostheses or direct expression of photosensitive proteins.