By Craig Smith, Eye & Ear Foundation Director of Development and Community Initiatives
Many diseases ultimately lead to blindness due to optic nerve damage. These include glaucoma, which damages the optic nerve, often through high ocular pressure; autoimmune diseases that cause demyelination of the optic nerve; vascular occlusions leading to damage from reduced blood flow; tumors or tissue growth that result in damage from immune infiltration or compressive injury; hereditary diseases that can lead to loss of retinal ganglion cells; and trauma to eye and orbit that can lead to optic nerve injury. The nerve can also be damaged from nutritional deficiencies or exposure to toxic chemicals.
The Louis J. Fox Center for Vision Restoration integrates a team of UPMC Vision Institute clinicians dedicated to treating and managing these conditions with the latest standards in clinical care, with University of Pittsburgh scientists studying these diseases and developing the next generation in vision-preserving therapies. Current therapies under development include drug and gene therapies to prevent the loss of ganglion cells and to promote the re-wiring of connections from the eye to the brain to restore visual function. The center also develops and conducts clinical trials with new therapies to test their efficacy in patients. Recently, the Fox Center expanded its research expertise by recruiting new faculty and developing strategic partnerships. Some key highlights of ongoing research include:
- Advancing optic nerve regeneration with Wake Forest. Dr. Takaaki Kuwajima, PhD, in the Department of Ophthalmology, in partnership with Dr. Stephen Badylak, DVM, PhD, MD, in the Department of Surgery, and Dr. Vijay Gorantla, MD, PhD, at Wake Forest University, recently concluded a study using a large animal model to show that by combining the work of Dr. Badylak and his membrane bound vesicles (MBVs) with the use of statins, particularly fluvastatin — a focus of Dr. Kuwajima’s work — was highly effective at protecting retinal ganglion cells and promoted some optic nerve regeneration. Faculty from both Pitt and Wake Forest are working on a full manuscript documenting their findings. While results were positive and may have a positive impact on the future of acute optic nerve injuries, researchers say that more work is needed to regenerate the optic nerve.
“This important study demonstrated that MBV and statins can be combined to keep ganglion cells alive from injury,” said Dr. John Ash, Vice Chair of Research at the University of Pittsburgh Department of Ophthalmology and Co-Director of the Fox Center. “This is an important step in the regrowth of the optic nerve. It’s important to note that the combination therapy is more effective than single therapies. This has broad implications for new therapy development. From all previous studies, we have about a dozen or more therapies that all show some level of regeneration, but not enough on their own. More work is needed to test additional combination therapies.”
- Advancing therapies for patients with optic nerve gliomas resulting from mutations in the Neurofibromatosis 1 (NF1) gene. NF1 patients can lose vision due to low-grade tumors growing on the optic nerve. The Department of Ophthalmology recently hired Dr. Silmara de Lima, PhD, to study the cellular and molecular mechanisms that cause optic nerve damage cause in these tumors and to develop novel therapies. Support for this work is provided through a partnership with the Gilbert Foundation. Dr. de Lima collaborates with Drs. Ash and Benowitz in these studies.
- Developing stem cell therapy to replace lost retinal ganglion cells. Dr. Kun-Che Chang, PhD, was involved in some of the first studies to develop retinal ganglion cells from human stem cells, and is now testing the ability of these cells to replace retinal ganglion cells that are lost after injury. One major obstacle in using stem cells is that they do not automatically form correct connections with other neurons in the retina or the brain. Dr. Chang is addressing this issue by using retinal organoids to identify key proteins that help ganglion cells find their correct targets.
- Developing new approaches for whole eye transplant. The University of Pittsburgh is a key part of a large multi-center consortium to establish protocols for functional vision recovery following the transplantation of the whole human eye. While the larger project includes multiple task groups focused on distinct problems facing whole eye transplantation, members of the Fox Center primarily focus on the most challenging hurdle: stimulating retinal ganglion cells to regenerate nerve fibers and reestablish appropriate connections in the brain. Researchers in the Department are now evaluating the efficacy of therapies previously reported to have partial effects and testing various combinations of these treatments, hoping to find the combination(s) that yield the most effective nerve fiber regrowth and restoration of functional vision. The Fox Center’s approach is to test about 25 different combinations of therapies in animal models of optic nerve crush and transection. In one model, the optic nerve is crushed, and therapies are used to repair it. In transectional models, the optic nerve is severed completely, and scientists attempt to regenerate and reconnect the two ends. The team is again working with Dr. Badylak to develop medicated nerve wraps to promote optic nerve healing and axon regeneration.
To accomplish these goals, the Department is looking to raise support for sustainable funding for the team of researchers in the Fox Center for Vision Restoration and to recruit additional faculty. The group also wants to establish funding for challenge grants to facilitate these efforts and get us over the finish line.