Update on Optic Nerve Regeneration Progress

graphic showing anatomy of the optic nerve

Leaders of the 2023 Louis J. Fox Center for Vision Restoration Conference shared the groundbreaking findings that were presented in October and talked about the future of vision restoration in the Eye & Ear Foundation’s November 10th webinar, “Update on Optic Nerve Regeneration Progress.”

The Louis J. Fox Center for Vision Restoration was established in 2009, with Louis and Dorothy Fox as the lead benefactors. The Fox Center team of researchers all focus on optic nerve regeneration at the University of Pittsburgh. Held October 10-11, this was the 13th annual Fox Center Symposium. It is focused on sharing research progress and establishing collaborations.

Eye Anatomy

Larry Benowitz, PhD, Professor of Ophthalmology at the University of Pittsburgh School of Medicine, Professor of Neurosurgery and Ophthalmology at Harvard Medical School, the Neurosurgical Innovation and Research Endowed Professor at Boston Children’s Hospital, and Co-Director of the Louis J. Fox Center for Vision Restoration, began his presentation by talking about the anatomy of the retina and optic nerve. Dr. Benowitz described the retina as the site where vision begins. “Through the precise connections involving millions of neurons, the retina itself is a marvelous computational device of extraordinary complexity,” he said.

Retinal ganglion cells (RGCs) are the output neurons of the eye whose nerve fibers connect through the optic nerve to visual relay centers in the brain. If that connection is interrupted as a result of traumatic injury or ischemic injury or in neurodegenerative diseases such as glaucoma, there is permanent loss because the optic nerve does not spontaneously regenerate. Immune-derived growth factors represent one way to stimulate optic nerve regeneration. He described his lab’s discoveries of several such growth factors and their recent identification of the receptor for one of these growth factors on RGCs, a protein called ArmC-10. Dr. Benowitz also mentioned some of the intracellular signaling pathways and transcription factors that suppress or activate the growth program in RGCs.

Fox Center Symposium

Just about every speaker at the symposium was a world leader in their respective field, Dr. Benowitz continued. A wide range of topics were covered that are relevant to solving the problem of promoting optic nerve regeneration.

Dr. Benowitz described each presentation. Here is a list of the speakers and their presentation titles:

  • Distinct Neutrophil Subsets Promote or Suppress Optic Nerve Regeneration, Roman Giger, University of Michigan
  • High-Throughput Screening to Identify Genes That Regulate RGC Survival and Axon Outgrowth, Derek Welsbie, University of California, San Diego
  • Reconnecting the Eyes to the Brain: Optic Nerve Regeneration and Functional Recovery, Xin Duan, University of California, San Francisco
  • Identification of the New Combination Regenerative Therapy, Taka Kuwajima and Stephen Badylak, UPMC Department of Ophthalmology
  • Neural Stem Cell Transplantation for Spinal Cord Injury, Jen Dulin, Texas A&M University
  • Human Stem Cell-Derived Retinal Ganglion Cells (RGCs) for Optic Nerve Regeneration, Donald J. Zack, Wilmer Eye Institute, Johns Hopkins University
  • Stem Cell and Neuroregeneration Laboratory, Kun-Che Chang, UPMC Department of Ophthalmology
  • Molecular Programs Underlying Retinal Development, Monica Vetter, University of Utah
  • Generation of a Mouse Model of NCRNA Disease to Understand the Disease Molecular Mechanism, Issam Al Diri, UPMC Department of Ophthalmology
  • Muller Glia Reprogramming and Retina Regeneration in Zebrafish, Goldman Lab, Tom Ray, University of Washington
  • Osteopontin (Spp1) Supports RGC Survival in a Mouse Model of Glaucoma, Yang Hu, Department of Ophthalmology, Stanford University
  • Intraocular Gene Therapy as a Therapeutic Strategy for Glaucoma, Meredith Gregory-Ksander, Schepens Eye Research Institute, Massachusetts Eye & Ear, Harvard Medical School
  • SARM1 Inhibitors: Protecting Axons to Preserve Vision, Aaron DiAntonio, Washington University (St Louis) Medical School
  • Harnessing Plasticity at the Reginogeniculate Synapse for Repair, Chinfei Chen, Boston Children’s Hospital, Harvard Medical School
  • High-Definition Retinal Structure, Angiography, and Oximetry with Vis-OCT, Shaohua Pi, Department of Ophthalmology, University of Pittsburgh

In the News

The day before the webinar, news broke of the world’s first whole eye transplant. As Dr. José-Alain Sahel, clinical spokesperson for the American Academy of Ophthalmology and Chair of the Department of Ophthalmology at the University of Pittsburgh School of Medicine, told CNN, “A key step in the whole eye transplant surgery was connecting Aaron’s optic nerve to the donor eye.”

While there is no evidence for any visual function at this stage, the surgery was successful in connecting the vessels in the eye. “A lot of the results that Larry was showing you is going to be extremely important in the future,” Dr. Sahel said. “We don’t know if this individual patient will benefit, but it is certainly a milestone on the path toward vision restoration.”

Immune tolerance of the donor eye is an important aspect of vision restoration through transplantation, and the results of the NYU study showed acceptable tolerance. However, restoring function will rely on regenerating the nerve fibers of the optic nerve, Dr. Sahel added. “The Fox Center is all about that, trying to reconnect the eye and brain and helping patients like this one who had no hope,” he said.