PDF(Pubmed)
Abstract：
The axons of retinal ganglion cells (RGCs) form the optic nerve, transmitting visual information from the eye to the brain. Damage or loss of RGCs and their axons is the leading cause of visual functional defects in traumatic injury and degenerative diseases such as glaucoma. However, there are no effective clinical treatments for nerve damage in these neurodegenerative diseases. Here, we report that LIM homeodomain transcription factor Lhx2 promotes RGC survival and axon regeneration in multiple animal models mimicking glaucoma disease. Furthermore, following N-methyl-D-aspartate (NMDA)-induced excitotoxicity damage of RGCs, Lhx2 mitigates the loss of visual signal transduction. Mechanistic analysis revealed that overexpression of Lhx2 supports axon regeneration by systematically regulating the transcription of regeneration-related genes and inhibiting transcription of Semaphorin 3C (Sema3C). Collectively, our studies identify a critical role of Lhx2 in promoting RGC survival and axon regeneration, providing a promising neural repair strategy for glaucomatous neurodegeneration.
摘要：
视网膜神经节细胞（RGC）的轴突形成视神经，将视觉信息从眼睛传递到大脑。RGC及其轴突的损伤或丢失是创伤性损伤和退行性疾病如青光眼中视觉功能缺陷的主要原因。然而,这些神经退行性疾病的神经损伤尚无有效的临床治疗方法。这里,我们报道LIM同源结构域转录因子Lhx2在多种模拟青光眼疾病的动物模型中促进RGC存活和轴突再生.此外，在N-甲基-D-天冬氨酸（NMDA）诱导的RGCs兴奋毒性损伤后，Lhx2减轻了视觉信号转导的损失。机制分析表明，Lhx2的过表达通过系统地调节再生相关基因的转录和抑制信号素3C（Sema3C）的转录来支持轴突再生。总的来说，我们的研究确定了Lhx2在促进RGC存活和轴突再生中的关键作用，为青光眼神经变性提供了一种有前途的神经修复策略。
