Research Continues to Yield Results, Even During Quarantine

Research never stopped at Salus University during the quarantine. In fact, researchers recently completed a large study that has been accepted for publication by the Journal of Biological Chemistry.

The study identified two clusters of surface-exposed amino acid residues that enable high-affinity binding of retinal degeneration-3 (RD3) protein to retinal guanylyl cyclase. Retinal degeneration causes various forms of congenital blindness.

“There are many proteins involved in signal transduction in the retina, so we’re studying the mechanisms of that process,” said Alexander Dizhoor, PhD, Hafter chair professor of Pharmacology at the University’s Pennsylvania College of Optometry (PCO), who along with Igor Peshenko, PhD, assistant professor at Salus PCO, authored the study. “As frequently happens when you study certain elements of the mechanism, it comes up that these elements are linked to certain diseases. Because if something goes wrong in the machinery that is perfectly tuned for certain purposes, like vision, you have an abnormal function of neurons, or loss of function. Or  an out-of-control function can kill the cell.” 

The University’s study of RD3 has been ongoing for the past nine years, which according to Dr. Dizhoor is a relatively short period of time compared to studying other proteins involved in photoreceptor signaling. 

“This is a relatively new protein for the field and only a handful of labs actually work with this protein at this time. So we were one of the first who studied biochemical properties of this protein,” he said.

The information gathered is important because it gives researchers a general idea how RD3 and its target protein in photoreceptor cells, retinal guanylyl cyclase, interact. 

“And, it also opens up the possibility to study some other functions of RD3 proteins that are not directly involved in binding to the cyclase but probably are involved in bringing target enzymes to the right place at the right time,” said Dr. Dizhoor.

Retinal guanylyl cyclase, the enzyme that RD3 regulates, has been implicated in many other genetic abnormalities causing blindness. The more researchers know about that enzyme, the better they can understand how it cab be approached to fix its activity using gene therapy designed to restore function of the diseased photoreceptor cells in the retina.

Researchers looked at only one part of the mechanism in this study. They’re also studying many other processes  related to normal vision and congenital retinal blindness. 

“We make mutations mimicking human disease and they become introduced into the mouse genome to see how it affects the function of photoreceptors in mice with the receptors in order to see how well we understand the mechanism. And, it create the models that would allow us test how to fix the problem in case of retinal disease,” said Dr. Dizhoor. “The purpose is not to make the mice blind, but to have a model that allows you to test how to fix blindness.”

Being on campus during the quarantine — even in a limited capacity and with a skeleton crew adhering to quarantine protocols established by the University — was necessary to complete the study.

“We were on campus on a limited basis because we are doing research with transgenic animals and cell cultures and things like that, which are really hard to put off,” said Dr. Dizhoor. “You cannot explain quarantine to mice or to cells growing on a culture dish, you have to deal with them all the time. The biochemical studies we conduct require our presence here. And, we never stopped our research, not for a single day.”

Dr. Dizhoor cited Dr. Peshenko’s dedication to his work during the quarantine period, together with the constant logistical support for the study provided by Lydia Parke, former assistant director of research who has since left the University, and by the Office of Research and Sponsored programs, which made it possible to accomplish the study despite the hurdles created by the COVID-19 outbreak.