Department of Neurobiology, Neuroscience Program, Fluminense Federal University, Niterói, RJ, Brazil.
Department of Anatomy and Cell Biology, Ophthalmology, and Physiology, University of Pennsylvania, Philadelphia, PA 19104, United States.
Brain Res Bull. 2019 Sep;151:92-108. doi: 10.1016/j.brainresbull.2018.10.016. Epub 2018 Nov 17.
Retinal injuries and diseases are major causes of human disability involving vision impairment by the progressive and permanent loss of retinal neurons. During development, assembly of this tissue entails a successive and overlapping, signal-regulated engagement of complex events that include proliferation of progenitors, neurogenesis, cell death, neurochemical differentiation and synaptogenesis. During retinal damage, several of these events are re-activated with both protective and detrimental consequences. Purines and pyrimidines, along with their metabolites are emerging as important molecules regulating both retinal development and the tissue's responses to damage. The present review provides an overview of the purinergic signaling in the developing and injured retina. Recent findings on the presence of vesicular and channel-mediated ATP release by retinal and retinal pigment epithelial cells, adenosine synthesis and release, expression of receptors and intracellular signaling pathways activated by purinergic signaling in retinal cells are reported. The pathways by which purinergic receptors modulate retinal cell proliferation, migration and death of retinal cells during development and injury are summarized. The contribution of nucleotides to the self-repair of the injured zebrafish retina is also discussed.
视网膜损伤和疾病是导致人类视力障碍的主要原因,其原因是视网膜神经元的进行性和永久性丧失。在发育过程中,组织的组装需要一系列连续且重叠的信号调节事件的参与,包括祖细胞的增殖、神经发生、细胞死亡、神经化学分化和突触形成。在视网膜损伤时,其中一些事件会被重新激活,产生保护和有害的后果。嘌呤和嘧啶及其代谢物正在成为调节视网膜发育和组织对损伤反应的重要分子。本综述概述了发育中和损伤的视网膜中的嘌呤能信号转导。本文报道了视网膜和视网膜色素上皮细胞中存在囊泡和通道介导的 ATP 释放、腺苷的合成和释放、嘌呤能信号转导在视网膜细胞中激活的受体和细胞内信号通路的表达。总结了嘌呤能受体在发育和损伤过程中调节视网膜细胞增殖、迁移和死亡的途径。还讨论了核苷酸对斑马鱼受损视网膜自我修复的贡献。