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Email You are free to share this article under the Attribution 4.0 International license. University University of California, Berkeley

Naturally occurring molecules known as lipid mediators could potentially halt the progress of glaucoma, new research suggests.

“We know of no drug that can do this.”

The world’s second-leading cause of blindness, glaucoma is a neurodegenerative disease in which fluid buildup in the frontal eye causes irreversible damage to the optic nerve and vision loss. At present, there is no cure for glaucoma, which is estimated to affect 80 million people worldwide.

“Not only could this discovery lead to drugs to treat glaucoma, but the same mechanism, and options for prevention, may be applicable to other neurodegenerative diseases,” says study senior author Karsten Gronert, professor of optometry and chair of vision science at University of California, Berkeley.

Preventing damage

Using rodent models, Gronert and fellow researchers found that inflammation-regulating lipid mediators known as lipoxins, secreted from star-shaped cells known as astrocytes, stopped the degeneration of retinal ganglion cells in rats and mice with glaucoma. Ganglion cells are the neurons of the retina and optic nerve that receive information from photoreceptors.

“We’ve taken something everyone assumed was anti-inflammatory, and found that these same small molecules play a key role in neuroprotection, which is really exciting,” says study co-senior author John Flanagan, dean and professor of optometry.

“This little-known lipid mediator has shown the potential to reverse cell death…”

Specifically, researchers found that astrocytes, which help maintain brain function and form the nerve fiber layer of the retina and optic nerve, release therapeutic biological agents known as lipoxins A4 and B4, but only when the astrocytes are at rest and maintaining nerve function.

“It is commonly assumed that astrocytes activated by injuries release stress signals that kill off ganglion cells in the retina, causing optic nerve damage,” says Flanagan. “However, our research discovered that astrocytes that are triggered by injury actually turn off novel neuroprotective signals that prevent optic nerve damage.”

Researchers discovered secretions of lipoxins A4 and B4 in resting astrocytes in culture in the retina and optic nerve head. To test their potential as a treatment, they administered the lipoxins to rodents eight weeks after the onset of glaucoma-like damage and neurodegeneration.

At 16 weeks, they gauged electrical activity in the rodents’ ganglion cells, among other measures, and found that lipoxin B4 in particular stopped the cells’ degeneration.

“This little-known lipid mediator has shown the potential to reverse cell death,” Gronert says. “We know of no drug that can do this.”

‘Great potential’

For decades, pharmaceutical companies have searched for neuroprotective drugs to treat glaucoma and other disorders marked by the death of nerve cells such as Alzheimer’s, Parkinson’s, and ALS. Glaucoma is by far the most prevalent of these neurodegenerative diseases.

“At the same time, lipoxins have been explored as promising drug targets for treating inflammatory diseases, but nobody has been looking at them as being neuroprotective,” Gronert says.

At present, the treatment option for glaucoma is to lower ocular pressure, but there are no effective treatments for preventing or stopping the neurodegeneration of glaucoma, which is irreversible and eventually leads to blindness, Flanagan says

The study authors are excited at the prospect of further investigations into the therapeutic benefits and mechanisms of lipoxins A4 and B4 and their potential to stop or reverse neural damage. They have jointly filed a patent application for use of lipoxins A4 and B4 to treat glaucoma and neurodegenerative diseases. Their eventual goal is to test the lipoxins as drugs in humans.

“These naturally occurring small lipids have great potential as therapies because they may play a fundamental role in preventing other neurodegenerative diseases. And that’s hugely significant, ” Flanagan says.

Additional researchers contributing to the study are from UC Berkeley and the University of Toronto.

The researchers detail their findings in the Journal of Clinical Investigation.

Source: Purdue University