Calcium-Signalling in Human Glaucoma Lamina Cribrosa Myofibroblasts

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 (Ca2+) 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 Ca2+ entry channels, Ca2+-dependent pumps and exchangers, and an abnormal rise in cytosolic Ca2+ in human glaucomatous LC fibroblast cells. We have evidence that this increase is dependent on Ca2+ 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 Ca2+-dependent mechanisms related to this abnormal Ca2+-signalling in human glaucoma LC cells, with a view toward identifying potential therapeutic targets for ongoing optic neuropathy.

Automated summary

Glaucoma is a common cause of treatable visual impairment, affecting millions of people worldwide. In this study, we investigated the role of calcium signaling in glaucomatous lamina cribrosa (LC) cells and found evidence of oxidative stress, mitochondrial dysfunction, and an abnormal rise in cytosolic calcium. This abnormal calcium signaling was dependent on calcium entry channels and released from internal stores in the endoplasmic reticulum and mitochondria. Further research in this area may help identify potential therapeutic targets for optic neuropathy.