Loss of Responses to Visual But Not Electrical Stimulation in Ganglion Cells of Rats With Severe Photoreceptor Degeneration
Loss of Responses to Visual But Not Electrical Stimulation in Ganglion Cells of Rats With Severe Photoreceptor Degeneration
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DOI：
10.1152/jn.00663.2009
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发表时间：
2009-12-01
影响因子：
2.5
通讯作者：
Chichilnisky, E. J.
中科院分区：
文献类型：
--
作者：
Sekirnjak, Chris;Hulse, Clare;Chichilnisky, E. J.
Sekirnjak C，Hulse C，Jepson LH，Hottowy P，Sher A，Dabrowski W，Litke AM，Chichilnisky EJ.严重光感受器变性大鼠神经节细胞对视觉刺激而非电刺激的反应丧失。J Neurophysiol 102：3260-3269，2009.首次发表于2009年9月2日; doi：10.1152/jn.00663.2009。视网膜植入物旨在通过电刺激存活细胞产生人工视觉来帮助退行性疾病患者。然而，很少有人知道如何个别视网膜神经节细胞的直接电刺激在退化的视网膜。在这里，我们使用了一个转基因大鼠模型来表征感光细胞变性过程中神经节细胞对光和电刺激的反应。在P37和P752年龄之间，将来自色素P23 H-1大鼠的视网膜与野生型视网膜进行比较。在变性过程中，视网膜厚度下降了50%，主要是由于感光细胞损失。视网膜神经节细胞的自发电活动最初增加了2 - 3倍，但在P600左右恢复到接近正常水平。在变性过程中观察到光响应神经节细胞数量的显著减少，在P550检测不到光响应的视网膜中达到顶峰。来自转基因和野生型动物的神经节细胞被靶向用于使用具有类似于10微米的电极直径的多电极阵列的局灶性电刺激。直接刺激神经节细胞，两组刺激成功率在所有年龄段均为60-70%。令人惊讶的是，P23 H大鼠神经节细胞的阈值（类似于0.05 mC/cm（2））和延迟（类似于0.25 ms）与所有年龄的野生型神经节细胞相当，并且没有随时间发生变化。因此，P23 H大鼠的神经节细胞对直接电刺激的反应正常，尽管光感受器严重退化，光反应完全丧失。这些研究结果表明，高分辨率视网膜前修复装置可能是有效的治疗视力丧失造成的感光细胞变性。
Sekirnjak C, Hulse C, Jepson LH, Hottowy P, Sher A, Dabrowski W, Litke AM, Chichilnisky EJ. Loss of responses to visual but not electrical stimulation in ganglion cells of rats with severe photoreceptor degeneration. J Neurophysiol 102: 3260-3269, 2009. First published September 2, 2009; doi:10.1152/jn.00663.2009. Retinal implants are intended to help patients with degenerative conditions by electrically stimulating surviving cells to produce artificial vision. However, little is known about how individual retinal ganglion cells respond to direct electrical stimulation in degenerating retina. Here we used a transgenic rat model to characterize ganglion cell responses to light and electrical stimulation during photoreceptor degeneration. Retinas from pigmented P23H-1 rats were compared with wild-type retinas between ages P37 and P752. During degeneration, retinal thickness declined by 50%, largely as a consequence of photoreceptor loss. Spontaneous electrical activity in retinal ganglion cells initially increased two- to threefold, but returned to nearly normal levels around P600. A profound decrease in the number of light-responsive ganglion cells was observed during degeneration, culminating in retinas without detectable light responses by P550. Ganglion cells from transgenic and wild-type animals were targeted for focal electrical stimulation using multielectrode arrays with electrode diameters of similar to 10 microns. Ganglion cells were stimulated directly and the success rate of stimulation in both groups was 60-70% at all ages. Surprisingly, thresholds (similar to 0.05 mC/cm(2)) and latencies (similar to 0.25 ms) in P23H rat ganglion cells were comparable to those in wild-type ganglion cells at all ages and showed no change over time. Thus ganglion cells in P23H rats respond normally to direct electrical stimulation despite severe photoreceptor degeneration and complete loss of light responses. These findings suggest that high-resolution epiretinal prosthetic devices may be effective in treating vision loss resulting from photoreceptor degeneration.