Department of Ophthalmology, Mater University Hospital, Eccles Street, D07F851 Dublin, Ireland.
Int J Mol Sci. 2023 Jan 9;24(2):1287. doi: 10.3390/ijms24021287.
Glaucoma is one of the most common causes of treatable visual impairment in the developed world, affecting approximately 64 million people worldwide, some of whom will be bilaterally blind from irreversible optic nerve damage. The optic nerve head is a key site of damage in glaucoma where there is fibrosis of the connective tissue in the lamina cribrosa (LC) extracellular matrix. As a ubiquitous second messenger, calcium (Ca) can interact with various cellular proteins to regulate multiple physiological processes and contribute to a wide range of diseases, including cancer, fibrosis, and glaucoma. Our research has shown evidence of oxidative stress, mitochondrial dysfunction, an elevated expression of Ca entry channels, Ca-dependent pumps and exchangers, and an abnormal rise in cytosolic Ca in human glaucomatous LC fibroblast cells. We have evidence that this increase is dependent on Ca entry channels located in the plasma membrane, and its release is from internal stores in the endoplasmic reticulum (ER), as well as from the mitochondria. Here, we summarize some of the molecular Ca-dependent mechanisms related to this abnormal Ca-signalling in human glaucoma LC cells, with a view toward identifying potential therapeutic targets for ongoing optic neuropathy.
青光眼是在发达世界中最常见的可治疗的视力损害原因之一，影响了全世界约 6400 万人，其中一些人将因不可逆的视神经损伤而双目失明。视神经头是青光眼损伤的关键部位，那里的筛板（LC）细胞外基质中的结缔组织发生纤维化。钙（Ca）作为一种普遍存在的第二信使，可以与各种细胞蛋白相互作用，调节多种生理过程，并导致多种疾病，包括癌症、纤维化和青光眼。我们的研究表明，在人青光眼 LC 成纤维细胞中存在氧化应激、线粒体功能障碍、钙内流通道、钙依赖性泵和交换器的表达升高以及细胞溶质钙的异常升高的证据。我们有证据表明，这种增加依赖于位于质膜中的钙内流通道，其释放来自内质网（ER）中的内部储存库，以及来自线粒体。在这里，我们总结了一些与人类青光眼 LC 细胞中这种异常钙信号相关的分子钙依赖性机制，以期确定正在进行的视神经病变的潜在治疗靶点。
