Model systems of photoreceptor degeneration: Anatomical and physiological characterization and establishment of stimulation paradigms

本项目的目的是建立一种方法，通过使用药理学调制和电调节的组合来改善视网膜神经节细胞的电刺激。我们第一个资助期的结果表明，在不同的视网膜色素变性动物模型中，视网膜显示出自发的节律性活动。与正常视网膜相比，退化视网膜中的神经节细胞电兴奋性较低。我们假设这种电兴奋性的降低与自发活动的出现有关。我们发现自发活动是通过阻断电突触来阻止的。初步结果表明，由电调节脉冲介导的强烈视网膜刺激允许在较长的时间段内改善神经节细胞的刺激。我们认为这些结果对BiMEA项目非常重要，并构成了我们新项目C部分的起点。我们将尝试在视网膜色素变性模型中准确评估视网膜变性的根本机制，并将联合收割机电调节脉冲与药物调制相结合。这将增强退化视网膜的电兴奋性，从而提高视网膜植入物的效率。因此，新项目C部分的实验结果对于新项目D部分的完成尤为重要。

The aim of this project is to establish a method, which improves electrical stimulation of retinal ganglion cells by using a combination of pharmacological modulation and electrical conditioning.The results of our first funding period indicate that in different animal models of retinitis pigmentosa the retina shows a spontaneous rhythmic activity. In comparison to normal retina, ganglion cells in degenerated retina are electrically less excitable. We assume that this decrease in electrical excitability correlates with the appearance of the spontaneous activity. We found that the spontaneous activity is prevented by blocking of electrical synapses. Preliminary results indicate that an intense retinal stimulation mediated by electrical conditioning pulses allow for an improved stimulation of ganglion cells over a longer period of time. We believe that these results are very important for the BiMEA project and form the starting point for our new project part C. We will try to exactly evaluate the fundamental mechanisms of the retinal degeneration in the model of retinitis pigmentosa and combine electrical conditioning pulses with pharmacological modulation. This should enhance the electrical excitability of the degenerated retina and thus improve the efficiency of retinal implants. Therefore, the experimental results of the new project part C are particularly important for the accomplishment of the new project part D.