Characteristic Patterns of Dendritic Remodeling in Early-Stage Glaucoma: Evidence from Genetically Identified Retinal Ganglion Cell Types
Characteristic Patterns of Dendritic Remodeling in Early-Stage Glaucoma: Evidence from Genetically Identified Retinal Ganglion Cell Types
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DOI：
10.1523/jneurosci.1419-14.2015
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发表时间：
2015-02-11
影响因子：
5.3
通讯作者：
Huberman, Andrew D.
中科院分区：
文献类型：
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作者：
El-Danaf, Rana N.;Huberman, Andrew D.
视网膜神经节细胞（RGC）的丧失是青光眼的标志，也是全球致盲的第二大原因。青光眼中导致RGC丢失的细胞变化的类型和时间仍然不完全清楚，包括特定的RGC亚型是否在该疾病的早期阶段优先受到影响。我们将青光眼微珠闭塞模型应用于不同的转基因小鼠系，每个系表达1-2个特定的RGC亚型的绿色荧光蛋白。靶向填充、重建和随后对对照组和头部注射眼中基因鉴定的RGCs的比较显示，一些亚型早在眼压升高（IOP）诱导后7天就发生了显著的树突重排。通过比较特定的On-type、On-Off-type和Off-type RGCs，我们发现将其大部分树突枝靶向于内丛状层（IPL）的巩膜半部分或“Off”层下的RGCs发生的变化最大，而大部分树突位于On-下层的RGCs在此时间点没有改变其结构。此外，M1本质光敏RGCs在功能上是On RGCs，但在结构上树突分层位于IPL的Off膜下，在IOP升高1周后树突结构也发生了显著变化。因此，我们的研究结果表明，某些RGC亚型在短暂暴露于IOP升高后，树突结构会发生显著变化。RGCs将其大部分树突分层，首先改变其结构，这一观察结果可能为人类青光眼检测、监测和治疗的新策略的发展提供信息。
Retinal ganglion cell (RGC) loss is a hallmark of glaucoma and the second leading cause of blindness worldwide. The type and timing of cellular changes leading to RGC loss in glaucoma remain incompletely understood, including whether specific RGC subtypes are preferentially impacted at early stages of this disease. Here we applied the microbead occlusion model of glaucoma to different transgenic mouse lines, each expressing green fluorescent protein in 1-2 specific RGC subtypes. Targeted filling, reconstruction, and subsequent comparison of the genetically identified RGCs in control and bead-injected eyes revealed that some subtypes undergo significant dendritic rearrangements as early as 7 d following induction of elevated intraocular pressure (IOP). By comparing specific On-type, On-Off-type and Off-type RGCs, we found that RGCs that target the majority of their dendritic arbors to the scleral half or "Off" sublamina of the inner plexiform layer (IPL) undergo the greatest changes, whereas RGCs with the majority of their dendrites in the On sublamina did not alter their structure at this time point. Moreover, M1 intrinsically photosensitive RGCs, which functionally are On RGCs but structurally stratify their dendrites in the Off sublamina of the IPL, also underwent significant changes in dendritic structure 1 week after elevated IOP. Thus, our findings reveal that certain RGC subtypes manifest significant changes in dendritic structure after very brief exposure to elevated IOP. The observation that RGCs stratifying most of their dendrites in the Off sublamina are first to alter their structure may inform the development of new strategies to detect, monitor, and treat glaucoma in humans.