PDF(Pubmed)
Abstract：
As part of the central nervous system, the optic nerve, composed of axons from retinal ganglion cells (RGCs), generally fails to regenerate on its own when injured in adult mammals. An innovative approach to promoting optic nerve regeneration involves manipulating the interactions between amacrine cells (ACs) and RGCs. Here, we identified a unique AC subtype, dopaminergic ACs (DACs), that responded early after optic nerve crush by down-regulating neuronal activity and reducing retinal dopamine (DA) release. Activating DACs or augmenting DA release with levodopa demonstrated neuroprotective effects and modestly enhanced axon regeneration. Within this context, we pinpointed the DA receptor D1 (DRD1) as a critical mediator of DAC-derived DA and showed that RGC-specific Drd1 overexpression effectively overcame subtype-specific barriers to regeneration. This strategy markedly boosted RGC survival and axon regeneration after crush and preserved vision in a glaucoma model. This study unveils the crucial role of DAC-derived DA signaling in optic nerve regeneration, holding promise for therapeutic insights into neural repair.
摘要：
作为中枢神经系统的一部分，视神经,由视网膜神经节细胞（RGCs）的轴突组成，在成年哺乳动物中受伤时，通常无法自行再生。促进视神经再生的创新方法涉及操纵无长突细胞（AC）和RGC之间的相互作用。这里,我们发现了一个独特的交流亚型,多巴胺能ACs（DACs），通过下调神经元活性和减少视网膜多巴胺（DA）释放，在视神经挤压后的早期反应。用左旋多巴激活DAC或增加DA释放显示出神经保护作用和适度增强的轴突再生。在此背景下,我们指出DA受体D1（DRD1）是DAC衍生的DA的关键介质，并表明RGC特异性Drd1过表达有效地克服了亚型特异性再生障碍。在青光眼模型中，这种策略显着提高了RGC存活和挤压后的轴突再生并保持了视力。这项研究揭示了DAC衍生的DA信号在视神经再生中的关键作用，对神经修复的治疗见解抱有希望。
