David Bissig received his doctoral degree in the Department of Anatomy and Cell Biology and is now completing the M.D. portion of his M.D./Ph.D. program.
Research led by a Wayne State University School of Medicine M.D./Ph.D. candidate is the first to document the effect of age on retinal calcium channels and declining vision.
The findings hint at a new approach for developing treatment for age-related vision problems in healthy individuals.
David Bissig’s work reveals a surprisingly strong relationship between retinal calcium channels and vision declines (or decreased vision). Previous studies documented age-related changes in retinal biology, but had difficulty linking those changes to vision declines. Bissig noted that in the brain neurons of older rats had more of a specific type of calcium channel than those of younger rats. This age-related increase in calcium channels is strongly linked to poor performance in memory tasks.
“We wondered if a similar process could explain why vision declines with age,” he said.
First, they measured younger rats’ visual function as well as ion entry through calcium channels using a special form of MRI. Several months later, they measured the rats’ vision a second time.
“Vision declined substantially in some rats, but other rats aged more gracefully, having relatively preserved visual function,” he said. “We found that ion entry greatly increased with age, and predicted how quickly vision degraded in the rats. Middle-aged rats with many open calcium channels in their retina tended to show the greatest vision declines between middle age and old age.”
Bissig received his doctoral degree in the Department of Anatomy and Cell Biology and is now completing the M.D. portion of his M.D. /Ph.D. program. “Diminished Vision in Healthy Aging Is Associated with Increased Retinal L-Type Voltage Gated Calcium Channel Ion Influx” was published in the Feb. 14 issue of the Public Library of Science ONE, an open-access journal of PLOS, a nonprofit publisher, member and advocacy group.
Like other cells, neurons have a membrane separating the inside of the neuron from the surrounding environment. “There are channels in this membrane that, when opened, allow calcium and other ions into a neuron,” he said.
The carefully-regulated passage of calcium into neurons impacts all aspects of neuronal function, including growth, death and neuron-to-neuron communication. Most ions that enter through these channels are pumped back out within seconds. The chemical element manganese, an MRI contrast agent, enters through calcium channels, but remains in a neuron from hours to days, he explained. To study retinal calcium regulation, the research team injects a non-toxic amount of manganese into a rodent, waits for it to accumulate in neurons and then measure manganese accumulation using magnetic resonance imaging.
“More manganese accumulation reflects more open channels in a neuron’s membrane. These channels open when neurons are active,” Bissig said. “With manganese-enhanced MRI, we are able to evaluate calcium channels non-invasively. This allows us to study the same rodent as it ages, and opens the possibility of using the same technique in translational human studies.”
Passage of ions through neurons’ calcium channels can be modified, but available drugs do this somewhat poorly, Bissig said. But more effective pharmaceuticals are being developed.
“The next step would be to test whether these newer pharmaceuticals can prevent vision declines in healthy aging,” he said.
Bissig is in the seventh year of the M.D./Ph.D. program, having completed his doctoral work and defended his doctoral dissertation in June 2012. He completed the work in the lab of Bruce Berkowitz, Ph.D., professor of Ophthalmology and Anatomy and Cell Biology, and the study’s senior author.
Dennis Goebel, Ph.D., associate professor of Anatomy and Cell Biology, also contributed to the work.
Bissig is especially appreciative of the support of the Department of Anatomy and Cell Biology Department, particularly chair Linda Hazlett, Ph.D., he said.The work was funded by an NIH F30 fellowship through the National Institute on Aging (AG034752), and the Wayne State University School of Medicine M.D./Ph.D. program.