Retinal ganglion cells (RGCs) are the only output neurons of the vertebrate retina, integrating signals from other retinal neurons and transmitting information to the visual centers of the brain. The death of RGCs is a common outcome in many optic neuropathies, such as glaucoma, demyelinating optic neuritis and ischemic optic neuropathy, resulting in visual defects and blindness. There are currently no therapies in clinical use which can prevent RGC death in optic neuropathies; therefore, the identification of new targets for supporting RGC survival is crucial in the development of novel treatments for eye diseases. In this study we identify that the receptor tyrosine kinase, Tyro3, is critical for normal neuronal function in the adult mouse retina. The loss of Tyro3 results in a reduction in photoreceptor and RGC function as measured using electroretinography. The reduction in RGC function was associated with a thinner retinal nerve fiber layer and fewer RGCs. In the central retina, independent of the loss of RGCs, Tyro3 deficiency resulted in a dramatic reduction in the number of RGC dendrites in the inner plexiform layer. Our results show that Tyro3 has a novel, previously unidentified role in retinal function, RGC survival and RGC morphology. The Tyro3 pathway could therefore provide an alternative, targetable pathway for RGC protective therapeutics.

中文翻译：

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Tyro3 有助于小鼠视网膜中的视网膜神经节细胞功能、存活和树突密度

视网膜神经节细胞 (RGC) 是脊椎动物视网膜唯一的输出神经元，它整合来自其他视网膜神经元的信号并将信息传输到大脑的视觉中心。RGC的死亡是许多视神经病变的常见结果，如青光眼、脱髓鞘性视神经炎和缺血性视神经病变，导致视力缺陷和失明。目前临床上还没有可以预防视神经病变中 RGC 死亡的疗法；因此，确定支持 RGC 存活的新靶点对于开发新的眼部疾病治疗方法至关重要。在这项研究中，我们确定受体酪氨酸激酶 Tyro3 对成年小鼠视网膜的正常神经元功能至关重要。Tyro3 的损失导致光感受器和 RGC 功能的减少，如使用视网膜电图测量。RGC 功能的降低与较薄的视网膜神经纤维层和较少的 RGC 相关。在中央视网膜中，与 RGC 的损失无关，Tyro3 缺陷导致内丛状层中 RGC 树突的数量急剧减少。我们的结果表明 Tyro3 在视网膜功能、研资局存活率和研资局形态方面具有新的、以前未知的作用。因此，Tyro3 通路可以为 RGC 保护性疗法提供替代的、可靶向的通路。Tyro3 缺陷导致内丛状层中 RGC 树突的数量急剧减少。我们的结果表明 Tyro3 在视网膜功能、研资局存活率和研资局形态方面具有新的、以前未知的作用。因此，Tyro3 通路可以为 RGC 保护性疗法提供替代的、可靶向的通路。Tyro3 缺陷导致内丛状层中 RGC 树突的数量急剧减少。我们的结果表明 Tyro3 在视网膜功能、研资局存活率和研资局形态方面具有新的、以前未知的作用。因此，Tyro3 通路可以为 RGC 保护性疗法提供替代的、可靶向的通路。