Lens homeostasis and transparency are dependent on the function and intercellular communication of its epithelia. While the lens epithelium is uniquely equipped with functional repair systems to withstand reactive oxygen species (ROS)-mediated oxidative insult, ROS are not necessarily detrimental to lens cells. Lens aging, and the onset of pathogenesis leading to cataract share an underlying theme; a progressive breakdown of oxidative stress repair systems driving a pro-oxidant shift in the intracellular environment, with cumulative ROS-induced damage to lens cell biomolecules leading to cellular dysfunction and pathology. Here we provide an overview of our current understanding of the sources and essential functions of lens ROS, antioxidative defenses, and changes in the major regulatory systems that serve to maintain the finely tuned balance of oxidative signaling vs. oxidative stress in lens cells. Age-related breakdown of these redox homeostasis systems in the lens leads to the onset of cataractogenesis. We propose eight candidate hallmarks that represent common denominators of aging and cataractogenesis in the mammalian lens: oxidative stress, altered cell signaling, loss of proteostasis, mitochondrial dysfunction, dysregulated ion homeostasis, cell senescence, genomic instability and intrinsic apoptotic cell death.

晶状体稳态和透明度取决于其上皮细胞的功能和细胞间通讯。虽然晶状体上皮独特地配备了功能性修复系统以承受活性氧 (ROS) 介导的氧化损伤，但 ROS 不一定对晶状体细胞有害。晶状体老化和导致白内障的发病机制有一个共同的主题；氧化应激修复系统的逐渐分解，驱动细胞内环境中的促氧化转变，累积 ROS 诱导的晶状体细胞生物分子损伤导致细胞功能障碍和病理。在这里，我们概述了我们目前对晶状体 ROS、抗氧化防御、以及维持晶状体细胞中氧化信号与氧化应激之间微调平衡的主要调节系统的变化。晶状体中这些氧化还原稳态系统的年龄相关性破坏导致白内障发生。我们提出了八个代表哺乳动物晶状体衰老和白内障发生共同特征的候选标志：氧化应激、细胞信号改变、蛋白质稳态丧失、线粒体功能障碍、离子稳态失调、细胞衰老、基因组不稳定性和内在细胞凋亡。