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In 2006, the first Catalyst For a Cure (CFC1) research team reported the development of three hypotheses for how glaucoma is initiated and where new therapeutic targets can be found.
Axonal degeneration — The first theory is derived from a fascinating event that occurs months or even years before nerve cells die in the retina. During the lifespan of a neuron, it continuously samples the microenvironment of its distal connections. In the case of a Retinal Ganglion Cell (RGC), this means that the cell is sampling the microenvironment of the brain by its longest process called the axon. It appears that the transport machinery or highway that RGCs use to bring neurotrophins — “food” really — back from the brain becomes dysfunctional early in the disease long before the RGC cell dies.
Gliosis — The second hypothesis is based on two primary observations. The CFC has found that there are distinct changes in the structure and functional state of glial cells in the glaucomatous retina. Glial cells get their name as a type of support cell or glue for the neurons, but until recently glial cells have not been adequately studied. The CFC has made an important finding that glial cells react very early in the progression of glaucoma by releasing proteins that may be toxic to neurons. The most exciting aspect of these data is that changes in glial cells appear to be the earliest event reported in the progression of glaucoma occurring well before vision begins to decline. This makes gliosis a potentially good therapeutic target.
Stretch injury — The final favored hypothesis is based on a family of molecules that have been discovered in the last 10 years and their genes are just being discovered. The molecules are called mechanical receptors and are located throughout the brain and retina and represent a complex family of molecules that are designed to sense stretch. Their presence in the retina has obvious implications for a disorder where pressure is clearly a cofactor the CFC proposes that these molecules may be what transmits a pressure signal into neuronal damage. Until this observation, the general concept was that pressure simply compressed the retina making it sick. These observations could provide a more specific mechanism for pressure-induced damage in the retina and, hence, one that could be specifically blocked therapeutically.
Article by Philip J. Horner, PhD, Assistant Professor of Neurological Surgery at the University of Washington in Seattle, and one of the four initial principal investigators of the GRF-funded Catalyst For a Cure research consortium.
Last reviewed on May 11, 2021