Using mice with high-pressure glaucoma, a team of researchers at the Vanderbilt Eye Institute (VEI) in Nashville determined that very early vision loss involves the loss of communication between the optic nerve and the mid-brain. Though conventional glaucoma treatments chiefly focus on reducing intraocular pressure, these findings suggest that future treatments could focus on altering neuronal activity in the middle of the brain, where the optic nerve forms its first connections.
“If you follow the disease long enough, eventually, the optic nerve, then the retina, shows signs of degeneration,” says lead author David J. Calkins, Ph.D., director of research at VEI. “So, the degeneration works in reverse order. It starts in the brain and works its way back to the retina so that in the very latest stages of the disease, the earliest structures—the ones nearest the eye—are the last to go.”
Using synthetic compounds and natural nerve growth factors, the research team currently is working to develop a therapeutic agent that could improve or restore the connectivity between the optics nerve and the mid-brain.
“The authors provide extensive evidence to support the hypothesis that a very early manifestation of retinal ganglion cell injury (in a mouse model) is a failure of active axonal transport, and that this abnormality occurs at a stage when retinal ganglion cells and their axons have yet to undergo complete degeneration,” says Brad Fortune, O.D., Ph.D., associate scientist and director of electrodiagnostic services at the Devers Eye Institute, in Portland, Ore.
“This point raises hope for developing methods to detect such abnormalities and institute therapeutic intervention in hopes of protecting retinal ganglion cells from further degeneration and death, perhaps even reversing this transport failure and other pathophysiological processes,” he says.
However, these study results will not likely change how clinicians manage glaucoma at this time, says Dr. Fortune.
“Although I anticipate the day when this data could lead to improved treatment options for glaucoma, especially for the most severe and rapidly progressive cases, that day is still far off in time and the practice of caring for glaucoma patients will continue to evolve slowly,” he says.
Crish SD, Sappington RM, Inman DM, et al. Distal axonopathy with structural persistence in glaucomatous neurodegeneration. Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5196-201.
