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Under pressure: Protecting neurons from glaucoma

The Jackson Laboratory News Jan 27, 2017

Pete Williams, PhD, is researching how to protect the optic nerve from changes in intraocular pressure caused by glaucoma, which would offer hope to patients suffering from gradual, irreversible vision loss.

There has been a long–standing puzzle in the field: why do glaucoma patients with normal eye pressure – either through medication or naturally – still experience gradual degeneration of the optic nerve? This fact suggests that there are other things going wrong in the neuron that contribute to its demise.

Williams is using a mouse strain that recapitulates the increased eye pressure and optic nerve damage seen in human patients. He’s looking for the earliest signs of damage in the neurons – changes that occur after eye pressure increases but before vision is lost.

“I want to figure out how to protect the neurons,” said Williams. His recent work goes in that direction. He’s identifying the genes that show changes in expression in the glaucoma–affected mice compared to their unaffected counterparts. Next, Williams will test which ones affect the symptoms. By disrupting those genes that are early contributors to the disease, Williams intends to prevent nerve degeneration.

Williams came across a surprisingly simple intervention based on the genes turned on in the mice that would eventually develop glaucoma. The list of genes contained many members of a particular metabolic process, suggesting to Williams that certain B vitamins and metabolites might be involved. He tested whether a simple dietary supplement could defend the nerves against glaucoma–associated damage, and so far, the results are encouraging. Williams is expanding this approach to include gene therapies that target the same metabolic pathways, exploring whether a single treatment could protect the optic nerve. He is collaborating with clinicians to see if his discoveries can help human patients.
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