GLAUCOMA RESEARCH

Research in neuroprotection in glaucoma appears to be on the wane, but it should be looked at with excitement, Francesca Cordeiro MD, PhD, told the 5th World Glaucoma Congress. Dr Cordeiro called on ophthalmologists to keep this area of research alive and noted that work in other areas of medicine show this is a promising and exciting area. "It's time we looked at colleagues in other fields," he said. "We have a lot to learn about neuroprotection and neuroregeneration in Parkinson's, Alzheimer's and stroke. Clinical trials in neuroprotection in glaucoma have been hit very badly and it's something we need to embrace as a community with industry, academia and other clinicians in trying to resurrect this potentially very rewarding area of research," said Dr Cordeiro, UCL professor of glaucoma and retinal neurodegeneration studies, London Institute of Ophthalmology, UK.

EuroTimes found Dr Cordeiro is not alone in her optimism. In a recent review of optic nerve-related research in the Canadian Journal of Ophthalmology (CJO), James C Tsai MD, Yale University noted that glaucoma is now considered a chronic, multi-factorial neurodegenerative disease of the central nervous system (CNS), and that future treatment and prevention techniques need to go beyond pressure-lowering. Strategies such as neuroprotection, neuro- enhancement and even neuroregeneration all show promise. It is also important to better understand what happens in the brain in glaucoma since along with retinal ganglion cell (RGC) death, there is atrophy and loss of neurons in parts of the brain. "But we won't get there if research isn't done," Dr Tsai told EuroTimes in an interview. Neuroprotection aims to prevent optic nerve head damage, RGC death or both, and lowering IOP is one neuroprotective strategy that has been very helpful. But causes of RGC death include ischemia, defects in axon communication, loss of electrical activity in the RGCs and more. Each cause presents a potential target for treatment, he said. Neuroprotection But which are the most promising areas for neuroprotection? Medication is one. Work with oral memantine, a neuroprotective agent used in Alzheimer's disease has not shown it to be helpful in glaucoma, but a recent trial suggested some neuroprotection occurred in glaucoma patients with topical brimonidine. It may do more than lower IOP. Several neurotrophic factors are being investigated in various neurodegenerative diseases and may have potential use in glaucoma, he said. Related to this, inhibitors of both Rho kinase (ROCK) and Rho GTPase enhance ocular blood flow, RGC survival, and axon regeneration. Animal studies suggest the Rho antagonist C3-07 helps repair and promotes nerve growth. Erythropoietin (EPO), a cytokine already used to treat anaemia, has neuroprotective effects in animal models of glaucoma by inhibiting programmed cell death or apoptosis. Some labs are testing gene therapy and stem cell implantation. A recent human phase-I safety trial demonstrated the successful delivery of CNTF (ciliary neurotrophic factor) to the back of the eye. Gene therapy has shown promise in promoting RGC survival in experimental models of optic nerve injury, Dr Tsai said.

Research from the University of Toronto showed that adult retinal stem cells can be programmed to produce photoreceptors. The same researchers also developed an injectable, biodegradable cell delivery system that successfully delivered stem cells to the sub-retinal space in mice. Nerve tissue Indeed, several approaches are being tested for the microencapsulation of compounds with the idea they would provide timed-release treatments that could protect the nerve, repair it or possibly even regenerate nerve tissue. Some work is even looking at electrical stimulation to improve the function of surviving nerve tissue. Immune system modulation may be another approach. While parts of the immune response in glaucoma can cause neural injury, there is some suggestion that other parts offer a protective role. The research in this area is fairly complex, Dr Tsai said.

In addition, some researchers are investigating tumour necrosis factor (TNFa), known to play a role in apoptosis, as a possible target. Another area of interest is neuroregeneration. The myelin around central nervous system cells contains compounds which inhibit nerve growth, and various research groups are trying to modulate or block these compounds. Several methods are being developed to deliver stem cells to replace RGCs and their axons to restore vision, said Dr Tsai, but neuroprotection by any of these means is likely 10 to 20 years away. “It’s not that we don’t have promising neuroprotective agents today, it's because we haven’t proven neuroprotection unequivocally in human clinical trials,” he said.