Eyeworld

EW GLAUCOMA 38 by Maxine Lipner EyeWorld Senior Contributing Writer Also exciting is that the en- zymes that make lipoxins are present throughout the brain and central nervous system. "We're able to show a similar type of action on other types of nerve cells from the cortex or the hippocampus, which are important for other neurode- generative diseases," he said. They hope what they've identified is part of a broad mechanism that has been unappreciated, where these types of molecules account for a healthy signal throughout the central ner- vous system that is being secreted by these support cells, Dr. Sivak ex- plained. "This signal becomes lost or dysregulated when there is an injury or a chronic disease process, and if we can restore it, we might be able to treat a broad variety of disease," he said. Interestingly, the precursors of the lipoxins are dietary, Dr. Sivak stressed. "There is a potential link that helps explain some sources of dietary differences in terms of dis- ease mechanisms and who is susceptible to different types of neurodegenerative disease," he said. These may also have an impact on diseases such as Alzheimer's or Parkinson's. "I am excited about the glaucoma angle," he said. "I think it has an exciting potential in a way that hasn't been exploited so far." Dr. Sivak said treating retinal degen- eration at the heart of the disease process is one of the next steps in glaucoma treatment. EW Reference 1. Livne-Bar I, et al. Astrocyte-derived lipoxins A4 and B4 promote neuroprotection from acute and chronic injury. J Clin Invest. 2017;127:4403–4414. Editors' note: Dr. Sivak has no finan- cial interests related to his comments. Contact information Sivak: jsivak@uhnres.utoronto.ca trial, and we only started to treat [the mice] at week 8, at which time we know that the nerve cells have already become damaged," Dr. Sivak said, adding that this resembles what happens when someone comes in with vision loss. Investigators found that when there is an injury or damage, the level of lipoxins goes down. They then injected lipoxins and found they were able to almost immediately halt the vision loss. "We restored [the lipoxins], and we did it by delivering this to the blood systemically in the animals as well as with eye injections, proving that they can get to the right place," he said. Clinical potential Dr. Sivak finds these results encour- aging. "This leads to the potential clinical implications that if we can repeat this in glaucoma patients, we might see a similar kind of activity," Dr. Sivak said. cells were secreting something that was protective. "When they became stressed, they stopped making what- ever this protective signal was, and we became intrigued by what that could be," Dr. Sivak said, adding that they later identified at least one important component of the signal as LXB4—one of a family of mole- cules called lipoxins. Unlike other neuroprotective factors, which are proteins, lipoxins are lipids derived from a derivative of omega-6 fatty acids known as arachidonic acid. "What is known about these mole- cules, the lipoxins, is that they have important roles in the rest of the body in helping to shut off inflam- mation," Dr. Sivak said. "But their role in the central nervous system is not well understood, and no one had appreciated that there might be some direct activity on neurons for these molecules." Investigators designed the recent study in a rat model to mimic a clinical trial. "It was a 15-week Potential neuroprotective treatment for glaucoma I nvestigators have identified a new neuroprotective factor that has the potential to help patients with glaucoma. In a study published in the Journal of Clinical Investigation, 1 a team of investigators at the University of Toronto and UC Berkeley found that with the aid of a unique molecule, called LXB4, neurons were protect- ed against the harmful effects of glaucoma in a preclinical model, according to Jeremy Sivak, PhD, associate professor, University of Toronto School of Medicine, and glaucoma research chair, University Health Network, Toronto. Rather than targeting glauco- ma risk factors, such as intraocular pressure, the researchers focused on preserving cells of the optic nerve, which connects the visual system to the brain. "My lab has been very interested in how to keep those cells alive and what might be causing them to be injured in the disease process," Dr. Sivak said. "There are no treatments that directly address that problem." Existing treatments for the disease are indirect and currently only aimed at pressure as a risk factor. Cell support crew Dr. Sivak has been studying inter- actions between the neuron cells that make up the optic nerve and neighboring support cells called astrocytes. Dr. Sivak likens these support cells to a pit crew for a For- mula One race car team. "The nerves are so specialized and so focused that they need their own support crew," he said. "There's an increas- ing amount of evidence [not only] from my own lab but from a variety of good researchers that dysfunction in the support system is part of the degenerative process." Investigators noticed that in their uninjured state, these support April 2018 Shielding neurons from harm Retinal ganglion cell neurons protected by LXB4 and stained using a fluorescent marker Source: Jeremy Sivak, PhD Research highlight

• Cover
• Blank Page
• Blank Page (1)