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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.
Glaucoma is a neurodegenerative disease that causes vision loss and blindness due to a damaged optic nerve.
“Age-related neurodegenerative disease, which includes glaucoma, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), is the biggest global health problem,” said principal investigator, Dr Arupratan Das.
“The fundamental mechanisms that we discovered can be used to protect neurons in glaucoma and be tested for the other diseases. We have identified a critical step of complex mitochondrial homeostasis process, which rejuvenates the dying neuron, similar to giving a lifeline to a dying person.”
Reversing Mitochondrial Damage
The research team, led by Michelle Surma and Kavitha Anbarasu from the Department of Ophthalmology, identified that glaucomatous retinal ganglion cells suffer mitochondrial deficiency with more metabolic burden on each mitochondrion. This leads to mitochondrial damage and degeneration. Mitochondria are the structures in cells that produce adenosine triphosphate, cell’s energy source.
However, the 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 adenosine triphosphate even with less mitochondria was astonishing,” Dr Das said.
“However, when triggered to produce more mitochondria, the adenosine triphosphate 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.
Reference
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.
This article has been republished courtesy of Mivision.
Researchers from the Indiana University School of Medicine hope to develop new glaucoma therapies by testing human neurons and a regenerative therapy to rescue dying visual neurons. They’ve received a new five year, US$2 million grant from the National Eye Institute for the project.
People of African ancestry are five times as likely as others to develop glaucoma and up to 15 times as likely to be blinded by the condition, but most research has used data from people of European ancestry.
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