University of Texas at San Antonio research recently revealed that it is the brain that controls the cellular process that causes glaucoma, and not the eye as thought until now. The findings have implications not only in the treatment of the disease, which causes irreversible blindness, but also for developing new therapies for diseases such as Alzheimer’s.
The study “Refined Data Analysis Provides Clinical Evidence for Central Nervous System Control of Chronic Glaucomatous Neurodegeneration” was led by William Eric Sponsel, MD, of the University of Texas at San Antonio, Department of Biomedical Engineering and published in Translational Vision Science & Technology. In the study, researchers performed a data and symmetry analysis of 47 patients with moderate to severe glaucoma in both eyes.
The researchers have found that the vision field works as an interlocking jigsaw puzzle, since when they examined the process of recovery of previously disabled optic nerve axons (the ones that lead to vision loss), they observed that the areas of permanent loss in one eye are the same areas that can still see in the other one.
Thus, this connection of the visual field enables much better vision with both eyes open, leading researchers to understand that the field of vision is determined by the brain. Until now, it was thought that glaucoma blindness was haphazard, not as a result of visual loss caused by neural damage within the brain as a result of strokes or tumors.
The researchers determined that the partial recovery of more diffuse overlapping visual field defects help unmask the more permanent interlocking jigsaw patterns, since the patients’ eyes were severely affected and had been surgically stabilized. “The extent and statistical strength of the jigsaw effect in conserving the binocular visual field among the clinical population turned out to be remarkably strong. The entire phenomenon appears to be under the meticulous control of the brain,” explains Sponsel.
“As age and other insults to ocular health take their toll on each eye, discrete bundles of the small axons within the larger optic nerve are sacrificed so the rest of the axons can continue to carry sight information to the brain,” stated the author. “This quiet intentional sacrifice of some wires to save the rest, when there are decreasing resources to support them all (called apoptosis), is analogous to pruning some of the limbs on a stressed fruit tree so the other branches can continue to bear healthy fruit,” he added.
The team of investigators discovered that the cellular process used for shortening small optic nerve axons in glaucoma is similar to the apoptotic mechanism found in the brains of patients with neurodegenerative diseases. “When shown the complementarily of their isolated right and left eye visual fields, they become far less perplexed and more reassured,” said Sponsel about the results of the patients’ analysis. “It would be relatively straightforward to modify existing equipment to allow for the performance of simultaneous binocular visual fields in addition to standard right eye and left eye testing.”
These findings may give clues to further investigations with cellular processes similar to the one used for pruning small optic nerve axons in glaucoma. The disease has much in common with neurodegenerative disorders, and the scholars hope that the research may also help understand more about connections of other nerves with the brain.
This is the first study revealing that the human brain plays an important role in pruning optic nerve axon cells. A previous study, Failure of Axonal Transport Induces a Spatially Coincident Increase in Astrocyte BDNF Prior to Synapse Loss in a Central Target, featured a mouse model revealing that the brain controlled a pruning of the injured optic cells in the eye at the end of the nerve, which would eventually cause the cells’ death.
“Our basic science work has demonstrated that axons undergo functional deficits in transport at central brain sites well before any structural loss of axons,” said David J. Calkins, PhD, of the Vanderbilt Eye Institute and author of the previous study. It was found no evidence of pruning of axon synapses until later. Likewise, the projection of neurons in the brain persists longer.