Aboelnour Asmaa, Van der Spuy Jacqueline, Powner Michael, Jeffery Glen
Histology and Cytology Department, Faculty of Veterinary Medicine, Damanhour University, Egypt.
Institute of Ophthalmology, University College London, UK.
Exp Eye Res. 2017 Dec;165:105-108. doi: 10.1016/j.exer.2017.09.013. Epub 2017 Sep 30.
Photoreceptor cells have high energy demands and suffer significantly with age. In aged rodents both rods and cones are lost, but in primates there is no evidence for aged cone loss, although their function declines. Here we ask if aged primate cones suffer from reduced function because of declining metabolic ability. Tau is a microtubule associated protein critical for mitochondrial function in neurons. Its phosphorylation is a feature of neuronal degeneration undermining respiration and mitochondrial dynamics. We show that total tau is widely distributed in the primate outer retina with little age-related change, being present in both rods and cones and their processes. However, all cones specifically accumulate phosphorylated tau, which was not seen in rods. The presence of this protein will likely undermine cone cell function. However, tau phosphorylation inhibits apoptosis. These data may explain why aged primate cones have reduced function but appear to be resistant to cell death. Consequently, therapies designed to remove phosphorylated tau may carry the risk of inducing cone photoreceptor cell death and further undermine ageing visual function.
光感受器细胞对能量需求很高，且随着年龄增长会受到显著影响。在老年啮齿动物中，视杆细胞和视锥细胞都会减少，但在灵长类动物中，尽管视锥细胞功能下降，但没有证据表明其数量会随年龄减少。在这里，我们探讨老年灵长类动物的视锥细胞功能下降是否是由于代谢能力下降所致。Tau是一种与微管相关的蛋白质，对神经元的线粒体功能至关重要。其磷酸化是神经元变性的一个特征，会破坏呼吸作用和线粒体动力学。我们发现，总Tau广泛分布于灵长类动物的视网膜外层，且与年龄变化关系不大，在视杆细胞和视锥细胞及其突起中均有存在。然而，所有视锥细胞都特异性地积累了磷酸化Tau，而视杆细胞中未观察到这种现象。这种蛋白质的存在可能会损害视锥细胞的功能。然而，Tau磷酸化可抑制细胞凋亡。这些数据可能解释了为什么老年灵长类动物的视锥细胞功能下降，但似乎对细胞死亡具有抗性。因此，旨在去除磷酸化Tau的疗法可能会有诱导视锥光感受器细胞死亡并进一步损害衰老视觉功能的风险。
