Glaucoma, a neurodegenerative disease stemming from a damaged optic nerve, causes vision loss and blindness. In the United States, over 200,000 people suffer from glaucoma yearly, though there is no cure.
The newly-published study was released in Communications Biology and outlined how researchers used neurons found in mitochondria as a steady source of energy, restoring homeostasis in the diseased neurons to protect the optic nerve cells.
Arupratan Das, Ph.D., Assistant Professor of Ophthalmology and the principal investigator of the study said, “Age-related neurodegenerative disease, which includes glaucoma, Parkinson’s disease, and Amyotrophic Lateral Sclerosis (ALS) is the biggest global health problem. 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 of the complex mitochondrial homeostasis process, which rejuvenates the dying neuron, similar to giving a lifeline to a dying person.”
Induced Pluripotent Stem Cells (iPSCs) from patients with and without glaucoma were used in the study, as well as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), which engineered human embryonic stem cells with glaucoma mutation.
Researchers identified glaucomatous retinal ganglion cells suffering from mitochondrial deficiency (which leads to damage and degeneration) using Stem Cell Differentiated Retinal Ganglion Cells (hRGCs) of the optic nerve, electron microscopy, and metabolic analysis. Mitochondria are the tube-like structures in cells that produce adenosine triphosphate, the cell’s energy source.
A pharmacological agent could reverse the process, which could enhance mitochondrial biogenesis. Researchers showed retinal ganglion cells as highly efficient in degrading negative mitochondria, producing more to regain homeostasis.
Das said, “Finding that retinal ganglion cells with glaucoma produce more adenosine triphosphate even with less mitochondria was astonishing. 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.”
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