Glaucoma is the world’s second leading cause of irreversible blindness. A neurodegenerative disease with no cure, glaucoma damages the optic nerve, causing progressive vision loss if left untreated. Scientists from Indiana University School of Medicine (IUSM), however, have found a new therapeutic target–namely, mitochondria–that they believe could improve current glaucoma treatment for better optic nerve protection. Learn what they discovered.*

Mitochondria and glaucoma

Mitochondria are tube-like mini-organs within our cells that make most of the energy needed for daily living in the form of adenosine triphosphate (ATP). ATP is a compound that supports processes like muscle contraction and nerve impulses. 

In their article in the journal Communications Biology, the scientists at IUSM explain that our nerve cells need more ATP than other cells do to transmit signals. Mitochondrial dysfunction in these cells is associated with neurodegenerative diseases such as glaucoma, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). 

Retinal ganglion cells (RGCs) that form the head of the optic nerve are among the central nervous system (CNS) cells that need steady ATP in order to function. Their greater energy needs make them highly susceptible to mitochondrial dysfunction. This dysfunction, which can be inherited through genetic mutation, can cause mitochondrial optic neuropathy and is common in people with normal-tension glaucoma.

Mitochondrial dysfunctions are widespread among various CNS disorders. Yet, the authors say we have little knowledge of “mitochondrial quality control,” or how to balance mitochondrial function and maintain stability, to protect nerve cells

What the researchers did

The researchers sought to identify factors that could improve RGC survival and be therapeutic for optic nerve diseases, like glaucoma, as well as benefit age-related RGC loss.

• Stem cells from people with and without glaucoma, and with glaucoma mutation, were differentiated into RGCs of the optic nerve, then studied with an electron microscope and subjected to metabolic analyses.

What they found

The researchers made a surprising discovery.

• RGCs impacted by glaucoma suffered mitochondrial deficiency, with each mitochondrion having to work harder to make ATP.
  • This deficiency leads to mitochondrial damage and deterioration.
• On the other hand, this degenerative process was reversed using a specific pharmacological agent to promote new mitochondria.
  • When using this agent, researchers observed RGC protection.

Das explained that having more mitochondria to distribute the energy burden in RGCs is like having more people carry a heavy stone. “Each person will have less pain and injury, just like each mitochondrion will have less difficulty and damage.”

What it means

In people with glaucoma, restoring mitochondrial balance in RGCs may protect optic nerve cells from damage.

“Age-related neurodegenerative disease…is the biggest global health problem,” said Das. “The fundamental mechanisms that we discovered can be used to protect neurons in glaucoma and be tested for other diseases. We have identified a critical step…which rejuvenates the dying neuron, similar to giving a lifeline to a dying person.”

*Indiana University School of Medicine. (2023, March 10). Researchers discover therapeutic target to aid in glaucoma treatment. https://medicine.iu.edu/news/2023/03/glaucoma-therapeutic-target