A new grant awarded to the West Virginia University School of Medicine will allow researchers to develop novel strategies for answering some of the most pressing and outstanding questions related to the pathogenesis of retinal disease.
The grant was awarded to the Departments of Ophthalmology and Visual Sciences and Biochemistry and Molecular Medicine by the National Eye Institute, National Institutes of Health. It will provide approximately $420,000 in funding over a period of two years. The project is led by Michael Robichaux, PhD, and Wen Tao Deng, PhD, assistant professors in the Departments of Ophthalmology and Visual Sciences and Biochemistry and Molecular Medicine.
“This new research grant from the National Eye Institute enables us to develop a cutting-edge research technology that will allow us to visualize the subcellular mechanisms that sustain vision and retinal health,” Dr. Robichaux said.
Robichaux explained that eyes rely on light-sensing cells known as photoreceptors and in order to stay healthy and function properly, these cells constantly manufacture proteins and ship them to the specific cellular compartment where they are needed. When this process breaks down and proteins get delivered to the wrong place in the cell, photoreceptors die, which can lead to blinding genetic diseases like retinitis pigmentosa.
“Our research will allow us to visually track these proteins in laboratory models using a glowing dye, as we utilize super-resolution microscopy to investigate and observe their movements in real time,” he explained. “Establishing how this mistrafficking of proteins occurs and how photoreceptor protein dynamics are altered in models of retinal disease is an essential step forward in the development of successful therapies for these devastating diseases.”
Dr. Deng specializes in a form of gene therapy known as adeno-associated virus (AAV) therapy, which utilizes a harmless, naturally occurring virus to deliver healthy, functional genes into patient cells. Deng and her team utilized AAV gene therapy in preliminary tests to deliver the instructions for the custom-tagged proteins. Once the glowing dye was injected into the laboratory model, the team was able to observe the protein travel to the correct cellular compartment.
“I am honored to contribute our AAV gene therapy expertise to support this project,” Dr. Deng said. “Reliable gene delivery is an important technical component that plays a crucial role in the imaging work performed by Dr. Robichaux and his team.”
Robichaux added that he hopes this research can serve as a significant stepping stone in better understanding the mechanisms behind protein trafficking in photoreceptor cells.
“Research in the field of photoreceptor cell biology has advanced tremendously over the past decade, and yet, much of the inner workings of these miraculous cells that initiate vision still elude us,” he said. “I believe that consistent effort toward the development of new research technologies and approaches will lead to new, critical insights that will benefit future patients for years to come.”
In addition to the work performed by Robichaux and Deng, this project will receive critical support from a team of student researchers, who will take the lead on conducting the experiments in the laboratory. These researchers are Brooke Brothers, Kristen Haggerty and Shannon Lyons, all of whom are PhD candidates in the Biochemistry and Molecular Medicine Graduate Program.
“Our student researchers play a critical role in our research process by allowing us to broaden our reach and scope, while also providing crucial hands-on training to the next generation of vision researchers,” Robichaux said.
“Collaborations like this, where each member of our team is able to contribute their individual expertise, are what allow us to move more efficiently toward meaningful scientific questions, and ultimately arrive at novel conclusions for future patients,” Deng added.
Robichaux said that the development of this research project would not be possible with the infrastructure and leadership of the WVU Visual Sciences Center of Biomedical Research Excellence, which was funded through a major $11 million grant from the National Institute of General Medical Sciences, an agency of the National Institutes of Health, in 2022.
To learn more about vision research at the WVU School of Medicine, visit medicine.hsc.wvu.edu/eye/research.