Diminished vision in healthy aging is associated with increased retinal L-type voltage gated calcium channel ion influx.
Diminished vision in healthy aging is associated with increased retinal L-type voltage gated calcium channel ion influx.
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DOI：
10.1371/journal.pone.0056340
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Berkowitz BA
中科院分区：
文献类型：
--
作者：
Bissig D;Goebel D;Berkowitz BA
大量证据表明，在与年龄相关的认知功能衰退中，海马区L型电压门控钙通道(L-VGCC)表达增加，并通过这些通道离子内流。在这里，我们问这个“钙假说”是否适用于神经视网膜：通过L-VGCC的增加是否与健康衰老中有充分证据但知之甚少的视力下降有关？在Long-Evans大鼠中，我们发现通过活体视网膜L-VGCC的离子通量显着增加(锰增强磁共振成像(MEMRI))，这与进行性视力下降(视动跟踪)纵向相关。重要的是，成年早期视网膜对Mn2+的摄取程度显著预示着以后视觉对比敏感度的下降。此外，与老化的海马区一样，药物不敏感的L-VGCC亚型(α1D)的视网膜表达增加-体内实验证实了这种模式，即对L-VGCC阻断的敏感性随着年龄的下降而下降。这些数据突出了视网膜和海马体老化之间的机制相似之处，并提高了新的治疗目标的可能性，以最大限度地减少健康老龄化期间的视力损失。
Extensive evidence implicates an increase in hippocampal L-type voltage-gated calcium channel (L-VGCC) expression, and ion influx through these channels, in age-related cognitive declines. Here, we ask if this “calcium hypothesis" applies to the neuroretina: Is increased influx via L-VGCCs related to the well-documented but poorly-understood vision declines in healthy aging? In Long-Evans rats we find a significant age-related increase in ion flux through retinal L-VGCCs in vivo (manganese-enhanced MRI (MEMRI)) that are longitudinally linked with progressive vision declines (optokinetic tracking). Importantly, the degree of retinal Mn2+ uptake early in adulthood significantly predicted later visual contrast sensitivity declines. Furthermore, as in the aging hippocampus, retinal expression of a drug-insensitive L-VGCC isoform (α1D) increased – a pattern confirmed in vivo by an age-related decline in sensitivity to L-VGCC blockade. These data highlight mechanistic similarities between retinal and hippocampal aging, and raise the possibility of new treatment targets for minimizing vision loss during healthy aging.
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