来自美国密歇根大学健康系统的研究人员研究了斑马鱼在遭受损伤后能够再生受损视网膜的机制，这一研究结果提示着有朝一日也能够人类身上发挥同样作用的新策略，从而潜在性地允许医生利用这些策略延缓或逆转诸如视网膜黄斑变性和青光眼之类的疾病。
基于以前的研究，密歇根大学分子和行为神经科学研究所教授Daniel Goldman与博士后研究员Jin Wan和Rajesh Ramachandran一起利用模式动物斑马鱼开展研究，发现肝素结合的类表皮生长因子(heparin binding epidermal growth factor-like growth factor, HB-EGF)在视网膜再生期间发挥着关键性作用。这一研究发现于2012年2月14日发表在《细胞》子刊《发育细胞》期刊上。
Goldman说，“我们发现这种因子足以激活整个过程。”
当斑马鱼视网膜受损时，HB-EGF就得以表达并启动一系列变化从而导致视网膜中已知为米勒神经胶质细胞(Müller glia)的某些细胞退回到干细胞状态，然后这些处于干细胞状态的细胞就能够再生新的细胞从而修复损伤。研究人员发现即便眼睛未受损时，HB-EGF也能促进米勒神经胶质细胞退回到干细胞状态。
Goldman说，下一步实验就是探索这种因子及其相关途径是否也能够在哺乳动物中促进米勒神经胶质细胞去分化和形成干细胞。(生物谷：towersimper编译)
doi:10.1016/j.devcel.2011.11.020
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HB-EGF Is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration
Jin Wan, Rajesh Ramachandran, Daniel Goldman
Müller glia (MG) dedifferentiation into a cycling population of multipotent progenitors is crucial to zebrafish retina regeneration. The mechanisms underlying MG dedifferentiation are unknown. Here we report that heparin-binding epidermal-like growth factor (HB-EGF) is rapidly induced in MG residing at the injury site and that pro-HB-EGF ectodomain shedding is necessary for retina regeneration. Remarkably, HB-EGF stimulates the formation of multipotent MG-derived progenitors in the uninjured retina. We show that HB-EGF mediates its effects via an EGFR/MAPK signal transduction cascade that regulates the expression of regeneration-associated genes, like ascl1a and pax6b. We also uncover an HB-EGF/Ascl1a/Notch/hb-egfa-signaling loop that helps define the zone of injury-responsive MG. Finally, we show that HB-EGF acts upstream of the Wnt/β-catenin-signaling cascade that controls progenitor proliferation. These data provide a link between extracellular signaling and regeneration-associated gene expression in the injured retina and suggest strategies for stimulating retina regeneration in mammals.
