Ophthalmologist and Physician-Scientist
The Future Possibility of Optic Nerve Regeneration

The Future Possibility of Optic Nerve Regeneration

In the past year, there has been more news about glaucoma research as researchers investigate ways to treat the disease more effectively and potentially prevent it altogether. Due to an aging population, the incidence of glaucoma is expected to increase in the years to come, making the research particularly important for the future vision health of people around the world. Researchers are looking into a variety of new treatment options for the disease, ranging from using stem cells to regrow nerve cells to actually effecting the regeneration of retinal ganglion cells. The latter approach has picked up some momentum, and one team recently had some success with optic nerve regeneration.

How to Promote Regeneration in the Human Nervous System

In general, the human nervous system has a limited ability to heal itself and regenerate after an injury or an illness that causes damage, such as glaucoma. The subsequent functional impairment can prove a significant personal and societal burden. Thus, researchers have devoted time and resources to understanding how the cells might be encouraged to regenerate more fully. In glaucoma, the degeneration of the retinal ganglion cells, which are used to transmit optic nerve signals from the eye to the brain, results in irreversible blindness. The possibility of regenerating these cells could lead to a functional cure for the damage caused by glaucoma.

A team at University of Nebraska Medical Center, led by Iqbal Ahmad, PhD, demonstrated it is possible to regenerate retinal ganglion cells in the in vitro setting. Their research, published in the July 2019 issue of the journal Development, used rodent models and effectively achieved regeneration of human nerve cells. The team found the key to regeneration in the mTOR signaling pathway. This specific pathway, which is present in different types of cells, plays a key role in promoting cell survival. When the pathway is activated in degenerated retinal ganglion cells, the regeneration process begins. The researchers used a microfluidic chamber system to investigate this process more closely and to begin to understand the pathway by which axons can regenerate once they are lost.


A Closer Look at the Specifics of the University of Nebraska Research

The researchers found the mTOR pathway is activated during the process of retinal ganglion cell differentiation and its signaling can be used to promote neurogenesis of human retinal ganglion cells. From that finding, it could be possible to recapitulate developmental mechanisms responsible for regenerating injured central nervous system cells. Such recovery could serve to reduce the effects of injury in diseases such as glaucoma or, better yet, recover function after it has been lost. In other words, people who have become blind as a result of glaucoma may be able to recover at least some of their vision.

Ahmad, who has more than 25 years of experience researching the use of stem cells, particularly in relation to neuronal regeneration, is excited about the potential of this finding. He stated that what separates this research from other attempts at neuron regeneration is the use of human adult pluripotent stem cells, which will make it much easier to translate the research into potential gene and drug therapies. His lab applied for a patent on the technology used in the study and plans to move forward by looking specifically at clinical applications. Previous studies have used rat and mice stem cells to create a better understanding of the processes involved, but they do not easily translate into clinical applications.

Additional Work in the Field of Retinal Ganglion Cell Regeneration

The Nebraska team is not the first to look at how to effectively regenerate retinal ganglion cells. A November 2016 article published in the journal Eye focused on research conducted by Ruhr University Bochum Department of Cell Physiology Director Dietmar Fischer surrounding IL-6-like cytokines to promote optic nerve regeneration, as well as neuroprotection in general. However, the use of cytokines has historically generated only moderate effects, possibly because of intrinsic signaling pathway inhibitors or a limited expression of appropriate receptors in neurons. Researchers did show that directly targeting the gp130 receptor, which is a common receptor among all cytokines resembling IL-6, could demonstrate stronger in vitro and in vivo axon regeneration in retinal ganglion cells.

The Eye article research demonstrated that continuous expression of hyper-IL-6 through intravitreal injection after a nerve injury promoted long-distance axon regeneration. Some axons were even witnessed growing through the optic chiasm six weeks after the initial injury with the use of hyper-IL-6. The treatment has the potential to aid in optic nerve regeneration caused by an injury and could also have applications in the treatment of glaucoma, particularly in terms of halting the progress of the disease and perhaps restoring vision. In addition, there is potential synergy between this form of treatment and other neuroprotective strategies such as PTEN knockout. With advancements such as these, and the recent study by Ahmad’s team, it appears nerve regeneration may be a possibility for the treatment of glaucoma even if clinical applications are still in the future.