A new study published in Communications Biology suggests that restoring and maintaining mitochondrial homeostasis in damaged neurons could protect optic nerve cells from harm and, as a result, prevent glaucoma development.
Talk about the role of mitochondria and glaucoma first.
Mitochondria are tube-like structures within cells that generate the primary energy source—adenosine triphosphate (ATP)—for most biochemical and physiological processes, including movement, growth, and homeostasis.
Dysfunctions in mitochondria are largely associated with central nervous system (CNS) disorders such as glaucoma.
Now talk about the study
Researchers utilized induced pluripotent stem cells (iPSCs) from patients with and without glaucoma, along with clustered regularly interspaced short palindromic repeats (CRISPR)-engineered human embryonic stem cells with glaucoma mutation.
What did they find?
They constructed a model consisting of stem cell differentiated human retinal ganglion cells (hRGCs) of the optic nerve, electron microscopy, and metabolic analysis. From this, the researchers discovered that glaucoma-containing RGCs had mitochondrial deficiency that lead to mitochondrial damage and degeneration.
Tell me more.
While the investigators discovered that hRGCs are activated when under mitochondrial stress to maintain homeostasis, they also found that the process could be reversed through the use of a pharmacological agent to enhance mitochondrial biogenesis.
Anything else about RGCs?
Indeed . . . RGCs were found to have a high capacity for degrading mitochondrial dysfunction while simultaneously creating new mitochondria to maintain homeostasis.
Takeaways?
The authors noted surprise in finding that glaucoma-containing RGCs produce more ATP, even with less mitochondria, and distribute more mitochondria to restore homeostasis.
They plan on further study to determine whether such mechanisms can be used in animal models, with the intent to progress to human trials to potentially develop novel clinical interventions for glaucoma and retinal disease.