Indiana University School of Medicine researchers have identified a new treatment target that could lead to a more effective treatment for glaucoma.
Glaucoma is a neurodegenerative disease that causes vision loss and blindness due to damage to the optic nerve. More than 200,000 people develop glaucoma in the United States each year. Unfortunately, there is currently no cure. In a newly published paper in Communication biologyThe researchers found that neurons use mitochondria as a constant source of energy, and restoring mitochondrial homeostasis in diseased neurons can protect optic nerve cells from damage.
“Age-related neurodegenerative disease, which includes glaucoma, Parkinson’s disease and amyotrophic lateral sclerosis (ALS), is the largest global health problem,” said Dr. “The underlying mechanisms we discovered can be used to protect neurons in glaucoma and tested for other diseases. We have identified a critical step in the complex process of mitochondrial homeostasis, which regenerates dying neurons, similar to giving a lifeline to a dying person.”
The research team, led by Michelle Surma and Kavitha Anparasu of the Department of Ophthalmology, used induced pluripotent stem cells (iPSCs) from patients with and without glaucoma, as well as short spaced alternating repeats (CRISPR) systemically engineered with infected human embryonic stem cells. with glaucoma. leap. Using differentiated retinal ganglion cells for stem cells (hRGCs) from the optic nerve, electron microscopy and metabolic analysis, the researchers determined that glaucoma retinal ganglion cells are mitochondria-deficient with a greater metabolic burden on each mitochondria. This leads to mitochondrial damage and degeneration. Mitochondria are the tube-like structures in cells that produce adenosine triphosphate, which is the cell’s energy source.
However, the process can be reversed by enhancing mitochondrial biogenesis with a pharmacological agent. The team showed that retinal ganglion cells are very efficient at breaking down bad mitochondria, but at the same time produce more to maintain homeostasis.
“Finding that retinal ganglion cells with glaucoma produce more ATP even with less mitochondria was amazing,” Das said. However, when stimulating the production of more mitochondria, the load of ATP production was distributed among more mitochondria which restored the physiology of the organelle. It is similar to the situation where a heavy stone is being carried by fewer people versus more people – each person will feel With less pain and injury, just like every mitochondria will suffer less hardship and damage.”
In the future, Das would like to test whether these mechanisms protect the optic nerve in susceptible animal models before testing them in humans in hopes that they may lead to new clinical interventions.
