Research Stimulus – The Lifeblood of Innovation

Sight + Sound, Spring 2022

The Department of Ophthalmology at the University of Pittsburgh has bestowed three second round grants funded by the Henry L. Hillman Foundation. The grant funding is part of a $20M gift made by the HLH Foundation designed to stimulate innovative ideas and cross-disciplinary collaborations within the Department and the University.

Rob Shanks, PhD, Associate Professor in the Department of Ophthalmology and Basic Science Director, Charles T. Campbell Ophthalmic Microbiology Laboratory, received $71,128 for one year. His project, “Treating Herpes Virus Simplex Keratitis – A New Approach,” addresses an unmet need in anterior eye care.

A major class of therapeutic drugs called “biologics” has had a huge positive impact on modern medicine. However, they are almost completely unused on the eye because they are washed away by tears and blinking. Dr. Shank’s group has developed an approach to temporarily anchor biologics on the surface of the eye long enough for them to provide therapeutic activity.

“The goal of this specific project is to use this anchoring system for the treatment of ocular inflammation due to viral infection,” he said. “We are teaming up with experts in our department such as virologist-immunologist Tony St. Leger, PhD, and virologist-antiviral expert Eric Romanowski, MS, to achieve our goals. The Hillman grant will allow us the seed money to push this project forward toward the development of new drugs for the eye.”

Leah Byrne, PhD, Morgan Fedorchak DiLeo, PhD, José Alain-Sahel, MD, and Joseph Martel, MD, received $202,289 for a two-year project called “Retinal-adhesive thermoresponsive gel for AAV-mediated gene delivery to the outer retina.”

Gene therapy is a highly promising approach for the treatment of retinal blinding diseases for the first time, said Leah Byrne, Assistant Professor of Ophthalmology at the University of Pittsburgh. Safe, efficient, and controlled gene delivery to the retina is crucial for its success but remains a significant challenge.

“We’ve formed a highly interdisciplinary team to address this major obstacle,” Dr. Byrne said. “Our project will develop an innovative delivery system to enable safe and efficient delivery of therapeutic genes to retinal cells from an intravitreal injection route. This project will lead to new therapies for many forms of inherited retinal degeneration.”

The third Hillman grant went to two scientists collaborating on a project as part of the Louis J. Fox Center for Vision Restoration. Taka Kuwajima, PhD, and Stephen Badylak, DVM, PhD, MD, received $414,825 – in addition to a donation from Mr. Louis Fox — for their two-year project, “Investigation of the neuroprotective and regenerative effects of Statin/MBV-combination therapy in the porcine injury model.” MVB stands for matrix-bound nanovesicles, which are attached to the extracellular matrix. Ocular trauma and optic neuropathies causing optic nerve degeneration and retinal ganglion cell (RGC) death are among the leading causes of blindness worldwide. Human RGCs lack regenerative capacity and do not recover from damage. There are no FDA-approved drugs or therapeutic strategies to maintain the optic nerve and RGCs or promote axon regeneration immediately after injury.

To solve this issue, Dr. Kuwajima, Research Assistant Professor of Ophthalmology at the University of Pittsburgh, has been working with Stephen Badylak, Professor of Surgery and Deputy Director, McGowan Institute for Regenerative Medicine, since 2020. They discovered that co-injections of statin and MBV show more robust RGC survival and axon regeneration when compared to treatment with either statin or MBV alone.

To establish therapeutic interventions for human patients, these results will be leveraged in a large animal model. Drs. Kuwajima and Badylak will be working with the ocular trauma team led by Dr. Vijay Gorantla of Wake Forest School of Medicine.

More grants will be given over the next few years as part of the agreement with the Henry L. Hillman Foundation.