Abstract
In human retina, photoreceptor cell death (PCD) is a slow but conspicuous event, which continues with aging. Rods die earlier than cones, the latter continue to alter in a subtle manner until advanced aging. This review summarizes the existing information on age-related changes in photoreceptor cells, especially cones and analyses the possible associated factors. Oxidative and nitrosative stress are involved in photoreceptor alterations, which may stem from light and iron toxicity and other sources. Lipid peroxidation in macular photoreceptor outer segments and mitochondrial aberrations are prominent in aging. It is important to understand how those changes ultimately trigger PCD. The redistribution of calbindin D-28K and long/middle-wavelength-sensitive opsin in the parafoveal and perifoveal cones, anomalies in their somata and axons are strong predictors of their increasing vulnerability with aging. Signs of reduced autophagy, with autophagosomes containing organelle remnants are seen in aging photoreceptor cells. Currently, mechanisms that lead to human PCD are unknown; some observations favour apoptosis as a pathway. Since cones appear to change slowly, there is an opportunity to reverse those changes before they die. Therefore, a full understanding of how cones alter and the molecular pathways they utilize for survival must be the future research goal. Recent approaches to prevent PCD in aging and diseases are highlighted.
摘要
在人类视网膜中, 感光细胞死亡 (photoreceptor cell death, PCD) 是一个缓慢而显著的过程, 并随着年龄的增长而持续。视杆细胞比视锥细胞死亡发生的更早, 但后者以微妙的方式继续改变, 直到老年。这篇综述总结了光感受器与年龄相关变化的现有资料, 特别是视锥细胞, 并分析了可能的相关因素。氧化和亚硝化应激与光感受器的改变有关, 这源于光和铁的毒性以及其他来源。黄斑光感受器外节脂质过氧化和线粒体畸变在衰老过程中尤为突出。重要的是要了解这些改变最终是如何触发PCD的。随年龄增加, 钙结合蛋白D-28K和长/中波长敏感视蛋白在中心凹旁和中心凹周围的视锥细胞中重新分布, 因此视锥细胞神经元胞体和轴突异常是易受损的强预测因子。在老化的光感受器中可以看到自噬减少的迹象, 自噬小体内含有细胞器残余物。目前, 导致人类PCD的机制尚不清楚;一些研究认为其通过细胞凋亡的信号通路。由于视锥细胞变化缓慢, 所以有机会在它们死亡之前逆转这些变化。因此, 全面了解视锥细胞是如何改变的, 视锥细胞赖以生存的分子信号传导通路是未来的研究目标。另外, 我们强调了近期关于防止 PCD在衰老以及疾病中的作用。
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Acknowledgements
The work was supported by grants from the DBT (BT/PR10195/BRB/10/589/2007), SERB (SERB-AS-27/2012) and CSIR (No. 37/1593/13/EMR-II), New Delhi, India. The eyes were procured from National Eye Bank, AIIMS via approval of Institute human Ethics Committee (No. IEC/NP-57/2010). The protocol adhered to the tenets of Helsinki Declarations. TEM work was done at SAIF-New Delhi, AIIMS.
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Nag, T.C. Pathogenic mechanisms contributing to the vulnerability of aging human photoreceptor cells. Eye 35, 2917–2929 (2021). https://doi.org/10.1038/s41433-021-01602-1
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