Catalysts for collaboration and cure

Key Points

In 2002 the Foundation's Scientific Advisory Board selected four investigative groups with the purpose of facilitating the rapid and efficient development of technologies pertinent to understanding the causes of glaucoma and identifying potential new treatments. The simplicity of the proposal also broke with research tradition as Brunner explains: "There were really only two requirements. One that applicants were required to shift their focus to glaucoma, away from the field they were currently working in and the second was to collaborate, effectively."

That formula brought together expertise in ophthalmology, neurobiology and developmental genetics and the CFC research team comprises Philip Horner PhD, University of Washington, Nicholas Marsh-Armstrong PhD, John Hopkins University, Monica Vetter PhD, Univeristy of Utah and David Calkins PhD, Vanderbilt.

The GRF's view of glaucoma has been steadily evolving over the past seven years as a result of the studies conducted by the CFC and other researchers. "Several years ago," said Brunner, "the CFC made the fundamental discovery that the retinal ganglion cells are alive for a long time after most scientists assumed they had gone. The team found that retinal ganglion cells lose essential functions long before they die. For example, they lose the ability to carry transported material both to and back from the brain long before they disappear from the retina. This means there may be a unique window of opportunity to boost their function before it's too late." These findings were published in a Journal of Neuroscience paper in 2008. ^1,2

Significant discoveries through collaboration

The CFC discovered that the cell death that causes vision loss in glaucoma has two distinct phases and that axonal degeneration precedes neuronal loss. These facts point to a therapeutic window for interventions, as Professor Philip Horner explains: "We are currently focusing on a mouse model of pigmentary glaucoma and one of the advantages that we have is that we can simultaneously analyse many different parameters with four labs being involved." This means that the group is able to focus on the earliest points at which the axon begins to manifest changes and each of the team are looking at a different element of that axonal element. For example, Dr Horner's lab is interested in how oxidative stress influences axon. Fellow researcher, Monica Vetter, is interested in the glial cells – the immune cell of the eye and she has shown that that cell becomes activated very early on in the disease. This is a good indicator that if activation can be prevented disease progression can be slowed.

The lab of Dr Nick Marsh-Armstrong is very interested in the genetic changes. An observation in the cells is that when they become stressed he has shown that they downregulate many of the genes that are important for ganglion cells when the disease gets a hold. That potentially could be reversed by stimulating master genes in the ganglion cells to try to get them to maintain themselves. Consequently, the team is working on a number of fronts as a focus primarily on the axon and how axon health can be improved.