Department of Biological Sciences, Vanderbilt University, 2325 Stevenson Center, Box 1820 Station B, Nashville, TN 37235, USA.
Department of Biological Sciences, Vanderbilt University, 2325 Stevenson Center, Box 1820 Station B, Nashville, TN 37235, USA.
Stem Cell Reports. 2017 Apr 11;8(4):831-842. doi: 10.1016/j.stemcr.2017.02.007. Epub 2017 Mar 9.
Current efforts to repair damaged or diseased mammalian retinas are inefficient and largely incapable of fully restoring vision. Conversely, the zebrafish retina is capable of spontaneous regeneration upon damage using Müller glia (MG)-derived progenitors. Understanding how zebrafish MG initiate regeneration may help develop new treatments that prompt mammalian retinas to regenerate. We show that inhibition of γ-aminobutyric acid (GABA) signaling facilitates initiation of MG proliferation. GABA levels decrease following damage, and MG are positioned to detect decreased ambient levels and undergo dedifferentiation. Using pharmacological and genetic approaches, we demonstrate that GABA receptor inhibition stimulates regeneration in undamaged retinas while activation inhibits regeneration in damaged retinas.
目前修复受损或患病的哺乳动物视网膜的方法效率低下，且在很大程度上无法完全恢复视力。相反，斑马鱼视网膜在受到损伤后，利用 Muller 胶质（MG）衍生的祖细胞能够自发地进行再生。了解斑马鱼 MG 如何启动再生，可能有助于开发促使哺乳动物视网膜再生的新疗法。我们发现，抑制γ-氨基丁酸（GABA）信号有助于启动 MG 增殖。损伤后 GABA 水平下降，而 MG 处于检测到环境中 GABA 水平下降并经历去分化的位置。我们通过药理学和遗传学方法证明，GABA 受体抑制可刺激未受损视网膜的再生，而激活则抑制受损视网膜的再生。
