Eyeworld

EW GLAUCOMA 113 Discovery could lead to medicinal therapies A new and surprising bio- logical pathway identify- ing the precise point where the cell damage oc- curs resulting in the loss of vision from glaucoma has been found by a team of researchers from the Kennedy Krieger Institute, Balti- more, as well as other collaborating institutions. The study, "Myelination transi- tion zone astrocytes are constitu- tively phagocytic and have synuclein dependent reactivity in glaucoma," was published in the Proceedings of the National Academy of Sciences. Using mouse models of glau- coma, Nicholas Marsh-Armstrong, Ph.D., senior study author and re- search scientist, Kennedy Krieger Institute, and colleagues have come up with what they believe to be three major developments in learn- ing how glaucoma blinds. "We think we have identified where precisely the lesion is," he said. "We are not saying this is the first thing that happens in glau- coma, we are saying that this is probably the irreversible step, the point at which the cells are perma- nently damaged, barring some major discovery that makes cells grow back and wire up correctly." Glaucoma isn't just an eye dis- ease; it's a neurodegenerative disor- der, killing retinal ganglion cells. Previous studies indicate that the optic nerve head is the location where the neurons' axons are dam- aged, thus playing a role in the de- velopment of glaucoma. The location of this event is not in the lamina region of the brain, where most clinicians would expect, how- ever. Rather, the researchers discov- ered that it's precisely behind the lamina that the damage occurs. "The reason we think this is be- cause we've discovered very strange biology unfolding at that location," Dr. Marsh-Armstrong explained. Part of this strange biology is re- flected in a class of cells called astro- cytes, which researchers found to play a key role in the blinding ef- fects of glaucoma. "That is a completely surprising finding and, as far as I know, has not been described before in any other neurodegenerative disease," said Dr. Marsh-Armstrong. In the same precise, anatomical location, the researchers found evi- dence of a type of protein called gamma-synuclein, which is similar to suspicious forms of alpha-synu- clein, a highly toxic protein well es- tablished for playing a central role in the development of Parkinson's disease. "This is an extremely exciting finding," said Dr. Marsh-Armstrong. "It suggests that this may be a shared mechanism between neu- rodegenerative disorders, particu- larly glaucoma and Parkinson's disease." Establishing a shared mecha- nism between these two disorders would be a huge breakthrough in the quest for medical therapies for glaucoma. "There are therapeutics that are out there in clinical practice already for Parkinson's disease," Dr. Marsh- Armstrong said. "The possibility that some of the interventions that are relevant for Parkinson's disease may also be relevant for glaucoma is something we are very excited about." "I think this is one of the most significant findings in basic glau- coma research in recent years and has a high potential to yield new ap- proaches to translation for human patients moving forward," said Jeffrey L. Goldberg, M.D., Ph.D., associate professor of ophthalmol- ogy, Bascom Palmer Eye Institute, University of Miami. Glaucoma has no cure and pa- tients are in desperate need of better therapies to control the disease. There are a number of therapies out there for Parkinson's that could be possible candidates for glaucoma as well, although Dr. Marsh-Armstrong thinks it's too early to speculate on what those therapies are. According to the Michael J. Fox Foundation, Parkinson's disease af- fects 5 million people worldwide, whereas glaucoma affects 60 million, according to the Glaucoma Research Foundation. However, the money spent on glaucoma research pales in comparison to that spent on Parkin- son's. It's true that Parkinson's is a more devastating and terminal dis- ease, affecting the entire body, but glaucoma remains the second lead- ing cause of blindness worldwide, which can also be highly destructive and even terminal in developing countries. "We understand a huge amount about how Parkinson's happens, but our understanding of how glaucoma happens is truly rudimentary," Dr. Marsh-Armstrong explained. "That's based on the fact that there has been extensive research on Parkinson's. There are thousands of papers on Parkinson's disease but very few pa- pers on glaucoma." Dr. Marsh-Armstrong hopes that this discovery will encourage other scientists to begin studying glau- coma, particularly the researchers who are already working on Parkin- son's. "Now that we understand some critical details about how the disease happens, I'm hoping that pharma- ceutical companies who may already have products in development for Parkinson's may have a renewed in- terest in glaucoma," he said. If all goes well and it turns out that the therapies already in clinical practice for Parkinson's disease can be used for glaucoma, Dr. Marsh- Armstrong projects that these thera- pies could be ready for glaucoma patients within 5 years. If re- searchers have to go through the en- tire process from basic findings all the way up to clinical trials, the timeline expands to more than a decade. Either way, it's a step in a posi- tive direction for glaucoma treat- ment. "We are very excited," Dr. Marsh-Armstrong said. "We've re- ceived positive feedback from scien- tists who also believe that this is a fundamentally new finding and will lead to a new direction for future glaucoma research." EW Editors' note: The physicians inter- viewed have no financial interests related to their comments. Contact information Goldberg: jgoldberg@med.miami.edu Marsh-Armstrong: mlustig@ spectrumscience.com February 2011 March 2011 by Faith A. Hayden EyeWorld Staff Writer Unexpected biological pathway in glaucoma found

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