Oliveira-Valença Viviane M, Bosco Alejandra, Vetter Monica L, Silveira Mariana S
Laboratory of Neurogenesis, Neurobiology Program, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, UT, United States.
Front Cell Dev Biol. 2020 Sep 17;8:581136. doi: 10.3389/fcell.2020.581136. eCollection 2020.
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 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发生程序，以协调多能祖细胞按顺序但重叠的波产生特定细胞类型。在这个程序中，视网膜神经节细胞（RGCs）是最早产生的细胞类型。RGCs是视网膜的最终输出神经元，对视觉和昼夜节律至关重要。在多个脊椎动物物种中已经确定了关键分子步骤，以调节这种细胞类型的能力、特化和终末分化。这涉及神经元特异性转录因子网络、染色质动力学调节剂和微小RNA。在哺乳动物中，RGCs及其视神经轴突在青光眼和其他视神经病变中会发生神经变性和丧失，导致不可逆转的视力丧失。RGCs和轴突无法再生，这进一步凸显了设计高效RGC替代策略的必要性。在这里，我们描述了脊椎动物中RGCs分化的基本分子途径，以及从晚期祖细胞产生这种早期细胞类型的能力窗口延长的实验操作。我们讨论了小鼠和斑马鱼视网膜神经元再生的最新进展，并讨论了作为青光眼等致盲疾病视力恢复治疗方法实现RGC再生的可能策略和障碍。
