Glaucoma research gives a glimpse of a novel neuroprotection mechanism

Written by Francesca Lake

Researchers at the Krembil Research Institute (ON, Canada) have identified a novel neuroprotective factor with potential to help treat glaucoma and other neurodegenerative diseases.
Glaucoma results in progressive, irreversible degeneration of the optic nerve and can lead to blindness. Affecting over 70 million people globally, there is no known cure and treatments are limited to reducing ocular pressure. Preventing neurodegeneration is thus a major research goal.

Previous research had shown that astrocytes and related microglia have a neuroprotective role following CNS injury; however, the precise mechanisms had not been elucidated. The new study utilized a model of the inner retina in a bid to understand this process.

Biochemical and metabolomics screening revealed that protection is mediated via the small lipid mediator LXB4 and, to a lesser extent, LXA4.

“We found that this tiny lipid molecule is normally present in healthy eyes and acts as a neuroprotective signal,” explained Jeremy Sivak (Krembil Research Institute). “Healthy eyes produce LXB4, but in diseased eyes its levels are reduced. We showed that by restoring LXB4 we can preserve injured nerve cells from dysfunction and death.”

Furthermore, they demonstrated that LXB4 had potential therapeutic benefit for treatment of neurodegeneration. “A particularly exciting part of this discovery is that we don’t think this effect is limited to glaucoma,” explained Sivak. “This neuroprotection extends to the central nervous system and could be applicable to a host of other neurodegenerative diseases.”

The team now intends to further investigate this mechanism and design potential methods for its activation in the clinic. They also hope to explore the application of this discovery to other neurodegenerative conditions, such as Alzheimer’s disease and Parkinson’s disease.

Sources: Livne-Bar I, Wei J, Liu HH et al. Astrocyte-derived lipoxins A4 and B4 promote neuroprotection from acute and chronic injury J Clin. Invest. doi:10.1172/JCI77398 (2017);