Retrograde Signaling in the Optic Nerve Is Necessary for Electrical Responsiveness of Retinal Ganglion Cells
Retrograde Signaling in the Optic Nerve Is Necessary for Electrical Responsiveness of Retinal Ganglion Cells
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DOI：
10.1167/iovs.12-11188
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发表时间：
2013-02-01
影响因子：
4.4
通讯作者：
Porciatti, Vittorio
中科院分区：
文献类型：
--
作者：
Chou, Tsung-Han;Park, Kevin K.;Porciatti, Vittorio
目的.我们在小鼠模型中研究了视神经逆行信号在视网膜神经节细胞（RGC）电反应中的作用。在氯胺酮/甲苯噻嗪麻醉下，43只4 ~ 6月龄C57 BL/6 J小鼠通过图形视网膜电图（PERG）测量RGC的电反应。在用利多卡因阻断轴突运输之前和之后的不同时间，在球后水平（2 μ L，40 μ g/μ L）或在上级丘水平（SC，1 μ L，40 μ g/μ L）记录PERG。PERG也被记录之前和之后的不同时间视神经压碎眼后1.5毫米，然后TUJ 1阳性RGC计数切除的视网膜。作为对照，在注射生理盐水或假视神经手术后也记录了PERG。记录利多卡因注射前及注射后相应时间点的明视闪光视网膜电图（FERG）和视觉诱发电位（FVEP）。利多卡因注射导致PERG振幅快速（眼球后类似于10分钟，SC 1小时）可逆性降低（>= 50%）。视神经挤压导致挤压后1个月PERG振幅迅速（10-20分钟）、不可逆转地降低（70-75%）、PERG潜伏期增加（>25%）以及RGC损失（88%）。利多卡因对FVEP无影响。对于所有手术，FERG均未改变。由于实验干预是在poststretinal水平（S），PERG的变化可能与改变供应的逆行交付的材料从SC。这意味着，逆行转运的目标衍生分子是必要的正常RGC电反应。早期PERG变化的时间过程与快速逆行轴突运输的速度一致。（Invest Ophthalmol维斯科学。2013;54：1236-1243）DOI：10.1167/iovs.12-11188
PURPOSE. We investigated the role of retrograde signaling in the optic nerve on retinal ganglion cell (RGC) electrical responsiveness in the mouse model.METHODS. Electrical response of RGC was measured by pattern electroretinogram (PERG) in 43 C57BL/6J mice 4 to 6 months old under ketamine/xylazine anesthesia. PERGs were recorded before and at different times after blockade of axon transport with lidocaine at either the retrobulbar level (2 mu L, 40 mu g/mu L) or at level of the superior colliculus (SC, 1 mu L, 40 mu g/mu L). PERGs also were recorded before and at different times after optic nerve crush 1.5 mm behind the eye, followed by TUJ1-positive RGC counts of excised retinas. As controls, PERGs also were recorded after either saline injections or sham optic nerve surgery. The photopic flash electroretinogram (FERG) and visual evoked potential (FVEP) also were recorded before lidocaine and at relevant times afterwards.RESULTS. Lidocaine injection caused rapid (retrobulbar similar to 10 minutes, SC 1 hour), reversible reduction of PERG amplitude (>= 50%). Optic nerve crush caused rapid (10-20 minutes), irreversible reduction of PERG amplitude (70-75%), increase of PERG latency (>25%), as well as RGC loss (88%) 1 month after crush. FVEP was unaltered by lidocaine. For all procedures, the FERG was unaltered.CONCLUSIONS. As experimental interventions were made at postretinal level(s), PERG changes were likely associated with altered supply of retrogradely-delivered material from the SC. This implies that retrograde transport of target-derived molecules is necessary for normal RGC electrical responsiveness. The time course of early PERG changes is consistent with the speed of fast retrograde axon transport. (Invest Ophthalmol Vis Sci. 2013;54:1236-1243) DOI:10.1167/iovs.12-11188