Differential Progression of Structural and Functional Alterations in Distinct Retinal Ganglion Cell Types in a Mouse Model of Glaucoma
Differential Progression of Structural and Functional Alterations in Distinct Retinal Ganglion Cell Types in a Mouse Model of Glaucoma
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DOI：
10.1523/jneurosci.5461-12.2013
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发表时间：
2013-10-30
影响因子：
5.3
通讯作者：
Wong, Rachel O. L.
中科院分区：
文献类型：
--
作者：
Della Santina, Luca;Inman, Denise M.;Wong, Rachel O. L.
眼内压（IOP）升高是青光眼的主要危险因素。使用微珠注射技术，以长期提高IOP的15或30天的小鼠，我们确定了不同类型的视网膜神经节细胞（RGCs）的视觉反应特性的早期变化，并与这些变化与神经元的形态细胞死亡前。微珠注射的眼睛显示减少视动跟踪以及细胞死亡。在这样的眼睛，多电极阵列记录显示，四个RGC类型显示不同的改变，在他们的光响应IOP升高。与其他RGC相比，关闭瞬态RGC在结构和功能组织方面表现出更快的下降。相比之下，虽然光诱发的反应OFF持续RGCs的扰动，这种细胞类型的树突状乔木保持完整。ON-瞬态和ON-持续RGCs具有正常的功能感受野大小，但其自发和光诱发的放电率降低。ON和OFF持续RGCs失去了兴奋性突触，否则结构正常的树突状乔木。总之，我们的观察结果表明，在可检测到的树突损失之前，RGCs的自发活动和光诱发反应发生了变化。然而，当树突回缩时，我们发现感受野中心的大小发生了相应的变化。重要的是，IOP升高的影响在不同RGC群体的结构和功能中并不一致，在相同的时间范围内受到这种挑战的不同RGC类型也不一致。
Intraocular pressure (IOP) elevation is a principal risk factor for glaucoma. Using a microbead injection technique to chronically raise IOP for 15 or 30 d in mice, we identified the early changes in visual response properties of different types of retinal ganglion cells (RGCs) and correlated these changes with neuronal morphology before cell death. Microbead-injected eyes showed reduced optokinetic tracking as well as cell death. In such eyes, multielectrode array recordings revealed that four RGC types show diverse alterations in their light responses upon IOP elevation. OFF-transient RGCs exhibited a more rapid decline in both structural and functional organizations compared with other RGCs. In contrast, although the light-evoked responses of OFF-sustained RGCs were perturbed, the dendritic arbor of this cell type remained intact. ON-transient and ON-sustained RGCs had normal functional receptive field sizes but their spontaneous and light-evoked firing rates were reduced. ON- and OFF-sustained RGCs lost excitatory synapses across an otherwise structurally normal dendritic arbor. Together, our observations indicate that there are changes in spontaneous activity and light-evoked responses in RGCs before detectable dendritic loss. However, when dendrites retract, we found corresponding changes in receptive field center size. Importantly, the effects of IOP elevation are not uniformly manifested in the structure and function of diverse RGC populations, nor are distinct RGC types perturbed within the same time-frame by such a challenge.