Retinal ganglion cell dysfunction induced by hypoxia and glutamate:: Potential neuroprotective effects of β-blockers
Retinal ganglion cell dysfunction induced by hypoxia and glutamate:: Potential neuroprotective effects of β-blockers
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DOI：
10.1016/s0039-6257(99)00054-5
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发表时间：
1999-06-01
影响因子：
5.1
通讯作者：
Wu, SM
中科院分区：
文献类型：
--
作者：
Gross, RL;Hensley, SH;Wu, SM
本研究的目的是研究缺氧、谷氨酸和β受体阻滞剂对视网膜神经节细胞电活动的影响。采用单细胞细胞外电压钳和全细胞电压钳记录技术，记录了虎蝾螈视网膜神经节细胞的电活动。这是在生理条件下，缺氧，或升高外源性或。内源性谷氨酸水平在β-1选择性拮抗剂倍他洛尔或非选择性拮抗剂噻吗洛尔存在下测量光诱发的尖峰活动、谷氨酸诱导的电流以及电压门控钠和钙电流。缺氧导致在大多数ON-OFF神经节细胞测试中抑制或阻断OFF反应，而ON反应仅受到轻微影响。谷氨酸增加的存在有类似的发现，并证明了视网膜神经节细胞自发放电率的增加。倍他洛尔（2-50 μ M）降低谷氨酸诱导的视网膜神经节细胞自发放电的速率。在2至50 μ M时，倍他洛尔可逆地降低视网膜神经节细胞中的电压门控钠电流和钙电流。噻吗洛尔（高达100 μ M）对这些电流未表现出任何可检测的作用。在该动物模型中，视网膜神经节细胞对缺氧或谷氨酸水平升高的生理反应似乎非常相似。虽然本研究中使用的短期暴露于缺氧和谷氨酸对神经节细胞产生可逆作用，并且不会诱导永久性细胞损伤，但这种初始生理作用可能是永久性细胞损伤的前兆。因此，视网膜中的缺氧和升高的谷氨酸水平可能代表影响视网膜神经节细胞的疾病如青光眼的最终途径。类似的损伤可能由不同的因素引起，例如灌注减少诱导的缺血或谷氨酸的异常神经元加工。倍他洛尔对视网膜神经节细胞发挥其初级神经元作用。它可逆地阻断电压门控钙电流，并通过抑制谷氨酸门控电流和钠电流降低神经节细胞的自发GRIN率。这些作用可以保护神经节细胞免受缺血引起的谷氨酸水平升高的损伤。(C)1999年，Elsevier Science Inc. All rights reserved.
The objective of this study was to examine the effects of hypoxia, glutamate, and beta-blockers on the electrical activities of retinal ganglion cells. Single-unit extracellular and whole-cell voltage clamp, recording techniques were used to record electrical activities from ganglion cells in the tiger salamander retina. This was performed under physiologic conditions, hypoxia, or elevated exogenous or. endogenous glutamate levels. Light-evoked spike activities, glutamate-induced currents, and voltage-gated sodium and calcium currents were measured ill the presence of the beta-1 selective antagonist betaxolol or the nonselective antagonist timolol. Hypoxia resulted in suppressing or blocking the OFF responses in the majority of ON-OFF ganglion cells tested, whereas the ON responses were only slightly affected. The presence of increased glutamate had similar findings and demonstrated an increase in the spontaneous firing rate of retinal ganglion cells. Betaxolol (2-50 mu M) reduced the rate of spontaneous firing of retinal ganglion cells induced by glutamate. At 2 to 50 mu M, betaxolol reversibly reduced the voltage-gated sodium currents and calcium currents in retinal ganglion cells. Timolol (up to 100 mu M) did not demonstrate any detectable action on these currents. The physiologic responses of retinal ganglion cells to hypoxia or elevated glutamate levels in this animal model appear to he very similar. Although short-term exposure to hypoxia and glutamate used in this study exerts reversible actions on ganglion cells and does not induce permanent cell damage, such initial physiologic actions are likely to be precursors of permanent cell damage. Thus, hypoxia and elevated glutamate levels in the retina may represent a final pathway ill diseases affecting retinal ganglion cells, such as glaucoma. Similar damage could result from different factors, such as decreased perfusion-induced ischemia or anomalous neuronal processing of glutamate. Betaxolol exerts its primary neuronal actions on retinal ganglion cells. It reversibly blocked voltage-gated calcium current and reduced the spontaneous Grins rate by suppressing glutamate-gated currents and sodium currents in ganglion cells. These actions may protect ganglion cells from damage caused by ischemia elevated glutamate levels. (C) 1999 by Elsevier Science Inc. All rights reserved.