Retinal development follows a conserved neurogenic program in vertebrates to orchestrate the generation of specific cell types from multipotent progenitors in sequential but overlapping waves. In this program, retinal ganglion cells (RGCs) are the first cell type generated. RGCs are the final output neurons of the retina and are essential for vision and circadian rhythm. Key molecular steps have been defined in multiple vertebrate species to regulate competence, specification, and terminal differentiation of this cell type. This involves neuronal-specific transcription factor networks, regulators of chromatin dynamics and miRNAs. In mammals, RGCs and their optic nerve axons undergo neurodegeneration and loss in glaucoma and other optic neuropathies, resulting in irreversible vision loss. The incapacity of RGCs and axons to regenerate reinforces the need for the design of efficient RGC replacement strategies. Here we describe the essential molecular pathways for the differentiation of RGCs in vertebrates, as well as experimental manipulations that extend the competence window for generation of this early cell type from late progenitors. We discuss recent advances in regeneration of retinal neurons in vivo in both mouse and zebrafish and discuss possible strategies and barriers to achieving RGC regeneration as a therapeutic approach for vision restoration in blinding diseases such as glaucoma.

视网膜发育遵循脊椎动物中保守的神经原性程序，以顺序但重叠的波协调多能祖细胞产生特定细胞类型的过程。在该程序中，视网膜神经节细胞（RGC）是第一个生成的细胞类型。RGC是视网膜的最终输出神经元，对于视觉和昼夜节律至关重要。已经在多种脊椎动物中定义了关键的分子步骤，以调节这种细胞类型的能力，规格和终末分化。这涉及神经元特异性转录因子网络，染色质动力学的调节剂和miRNA。在哺乳动物中，RGC及其视神经轴突会发生神经退行性变以及青光眼和其他视神经病变的丧失，从而导致不可逆的视力丧失。RGC和轴突无法再生，这增强了对设计有效RGC替换策略的需求。在这里，我们描述了在脊椎动物中RGC分化的基本分子途径，以及扩展了从晚期祖细胞生成这种早期细胞类型的能力窗口的实验操作。我们讨论了视网膜神经元再生的最新进展体内 在小鼠和斑马鱼中讨论了实现RGC再生的可能策略和障碍，作为在诸如青光眼等致盲疾病中恢复视力的治疗方法。