A team of researchers from the Indiana University School of Medicine have pinpointed a new therapeutic target that may result in a more effective treatment for glaucoma.
“Age-related neurodegenerative disease, which includes glaucoma, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS), is the biggest global health problem,” said Arupratan Das, PhD, assistant professor of ophthalmology and principal investigator of the study via a press release about the study. “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.”
Researchers assessed induced pluripotent stem cells (iPSCs) from patients with and without glaucoma, as well as clustered regularly interspaced short palindromic repeats (CRISPR) engineered human embryonic stem cells possessing a glaucoma mutation. The investigators utilized stem cell differentiated retinal ganglion cells (hRGCs) of the optic nerve, and electron microscopy and metabolic analysis. They found glaucomatous retinal cells contain mitochondrial deficiency with more metabolic burden on each mitochondrion, thereby resulting in damage and degeneration.
However, the researchers suggest that thus deleterious process could be reversed by enhancing mitochondrial biogenesis by a pharmacological agent. The researchers demonstrated that 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.”