The Wnt Signaling Pathway Protects Retinal Ganglion Cell 5 (RGC-5) Cells from Elevated Pressure
The Wnt Signaling Pathway Protects Retinal Ganglion Cell 5 (RGC-5) Cells from Elevated Pressure
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DOI：
10.1007/s10571-010-9603-z
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Hackam, Abigail S.
中科院分区：
文献类型：
--
作者：
Fragoso, Miryam A.;Yi, Hyun;Hackam, Abigail S.
Wnt 通路是调节视网膜存活和分化的重要信号级联。我们最近证明视网膜神经节细胞（RGC）在体内具有持续活跃的 Wnt 信号传导。然而，Wnt 在 RGC 活力或功能中的作用尚不清楚。在这项研究中，我们研究了 Wnt 是否可以保护视网膜神经节细胞系 RGC-5 免受高压、氧化应激和缺氧损伤。通过免疫细胞化学和 PCR 证实了 RGC-5 培养物中 RGC 标记基因的表达。我们证明，Wnt3a 配体显着降低了 RGC-5 细胞中压力诱导的 caspase 活性 (n = 5，P = 0.03)，并减少了 TUNEL 阳性细胞的数量 (n = 5，P = 0.0014)。值得注意的是，Wnt3a 依赖性保护可被 Wnt 信号抑制剂 Dkk1 逆转。相比之下，Wnt3a 不能保护 RGC-5 细胞免受氧化应激或缺氧的影响。此外，Wnt3a 在压力升高的情况下显着增加生长因子的表达，但在氧化应激和缺氧的情况下则不然。这些结果表明，Wnt3a 可能通过上调神经保护性生长因子来诱导 RGC-5 细胞中损伤特异性的生存途径。因此，可以进一步研究 Wnt3a 对 Wnt 通路的激活，作为开发预防视网膜疾病中 RGC 死亡的新型分子治疗策略的工具。
The Wnt pathway is an essential signaling cascade that regulates survival and differentiation in the retina. We recently demonstrated that retinal ganglion cells (RGCs) have constitutively active Wnt signaling in vivo. However, the role of Wnt in RGC viability or function is unknown. In this study, we investigated whether Wnt protects the retinal ganglion cell line RGC-5 from elevated pressure, oxidative stress, and hypoxia injuries. Expression of RGC marker genes in the RGC-5 cultures was confirmed by immunocytochemistry and PCR. We demonstrated that the Wnt3a ligand significantly reduced pressure-induced caspase activity in RGC-5 cells (n = 5, P = 0.03) and decreased the number of TUNEL-positive cells (n = 5, P = 0.0014). Notably, Wnt3a-dependent protection was reversed by the Wnt signaling inhibitor Dkk1. In contrast, Wnt3a did not protect RGC-5 cells from oxidative stress or hypoxia. Furthermore, Wnt3a significantly increased growth factor expression in the presence of elevated pressure but not in the presence of oxidative stress and hypoxia. These results indicate that Wnt3a induces injury-specific survival pathways in RGC-5 cells, potentially by upregulating neuroprotective growth factors. Therefore, activation of the Wnt pathway by Wnt3a could be investigated further as a tool to develop novel molecular therapeutic strategies for the prevention of RGC death in retinal disease.