Representative picture showing the number of cultured RGCs surviving an injury in the absence(left) or presence (right)of the neuroprotective agent.
Glaucoma is a disease in which the eye’s retinal ganglion cells (RGCs) are injured and die, in part due to effects of increased eye pressure. RGCs are the nerve cells that send visual information from the retina to the brain. Currently, all therapies for glaucoma center on lowering the eye pressure, which is effective, but difficult to achieve for some patients.
The hope for nerve cell protective therapy (called neuroprotection) that will complement pressure-lowering is closer this year thanks to research in the Glaucoma Center of Excellence by Drs. Derek Welsbie and Donald Zack. They found a way to interfere with the RGC cell death process in laboratory experiments published in the prestigious Proceedings of the National Academy of Sciences. The paper won a national award for Dr. Welsbie as most Innovative Research in Glaucoma 2014.
To find this new neuroprotective pathway, they developed a way to screen many possible drugs very quickly for their effect on cultured RGCs. Without treatment, cultured RGCs die quickly, but in their screening test a few agents dramatically slowed RGC death. Among 15,000 compounds, a group called kinase inhibitors were highly neuroprotective.
They paired this technique with a second innovative approach in which drugs were tested for their ability to inhibit each of the 17,000 genes in mice. This showed how the kinase inhibitors work to save RGCs.
This year, they have identified several candidate drugs that are highly effective at preserving RGCs in animal models
of glaucoma. Next steps: final animal trials followed by controlled testing in patients for the first neuroprotection treatment.
Researching Nerve Cells at the Wilmer Eye Institute (View Video)