Müller Glia maintain their regenerative potential despite degeneration in the aged zebrafish retina.
Müller Glia maintain their regenerative potential despite degeneration in the aged zebrafish retina.
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作者：
老化是视网膜变性的一个重要危险因素。Müller胶质细胞（MG）是神经元再生的关键，因此利用MG在视网膜中的再生能力为治疗年龄相关性致盲疾病提供了巨大的希望。然而，老化对MG再生能力的影响尚不清楚。在这里，我们表明斑马鱼视网膜经历端粒酶非依赖性，年龄相关性神经变性，但这不足以刺激MG增殖和再生。相反，年龄相关的神经退行性变伴有MG形态学畸变和视力丧失。从机制上讲，是相关蛋白（雅普），河马信号的一部分，已被证明是在受损的视网膜再生反应的关键，我们表明，雅普的表达水平随着年龄的增长而下降。尽管如此，形态和分子改变的老化MG保留了在急性光损伤后再生神经元的能力，因此，突出了MG对斑马鱼视网膜中高强度急性损伤与慢性神经元损失的反应的关键差异。我们的数据表明，老化的，分子和形态学改变的MG仍然可以刺激再生，以应对急性损伤，突出MG反应的关键差异相比，在老化的慢性损伤。
Ageing is a significant risk factor for degeneration of the retina. Müller glia cells (MG) are key for neuronal regeneration, so harnessing the regenerative capacity of MG in the retina offers great promise for the treatment of age‐associated blinding conditions. Yet, the impact of ageing on MG regenerative capacity is unclear. Here, we show that the zebrafish retina undergoes telomerase‐independent, age‐related neurodegeneration but that this is insufficient to stimulate MG proliferation and regeneration. Instead, age‐related neurodegeneration is accompanied by MG morphological aberrations and loss of vision. Mechanistically, yes‐associated protein (Yap), part of the Hippo signalling, has been shown to be critical for the regenerative response in the damaged retina, and we show that Yap expression levels decline with ageing. Despite this, morphologically and molecularly altered aged MG retain the capacity to regenerate neurons after acute light damage, therefore, highlighting key differences in the MG response to high‐intensity acute damage versus chronic neuronal loss in the zebrafish retina. Our data show that aged, molecularly and morphologically altered MG can still be stimulated to regenerate in response to an acute damage, highlighting key differences in MG response when compared to the chronic damage in ageing.
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