Researchers have identified a therapeutic target that could lead to more effective treatment of glaucoma.
In a paper published in Communications Biology,1 the researchers from Indiana University said neurons use mitochondria for a steady source of energy, and restoring mitochondrial homeostasis in the diseased neurons can protect the optic nerve cells from being damaged.
The researchers identified that glaucomatous retinal ganglion cells suffer mitochondrial deficiency with more metabolic burden on each mitochondrion. This leads to mitochondrial damage and degeneration. Mitochondria produce adenosine triphosphate (ATP), the cell’s energy source.
This process could be reversed by enhancing mitochondrial biogenesis by a pharmacological agent. The team showed retinal ganglion cells are highly efficient in degrading bad mitochondria, but at the same time producing more to maintain homeostasis.
“Finding that retinal ganglion cells with glaucoma produce more ATP even with less mitochondria was astonishing,” said principal investigator, Dr Arupratan Das.
“However, when triggered to produce more mitochondria, the ATP production load was distributed among more mitochondrion, which restored the organelle physiology. It is similar to a situation where a heavy stone is carried by fewer people versus a greater number of people — each person will have less pain and injury, just like each mitochondrion will have less difficulty and damage.”
In the future, Dr Das would like to test if these mechanisms protect the optic nerve in animal models under injury before testing in humans to hopefully lead to new clinical interventions.
1. Surma, M., Anbarasu, K., Dutta, S. et al. Enhanced mitochondrial biogenesis promotes neuroprotection in human pluripotent stem cell derived retinal ganglion cells. Commun Biol 6, 218 (2023). doi.org/10.1038/s42003-023-04576-w.
