Research conducted by scientists based at the University of California San Diego and the Stanford University School of Medicine has shown that crushed optic nerve cells can be re-grown in vivo to a level of partial functional vision by using a combination of visual stimulation and gene therapy. The research, conducted on rodent models, showed that the activity of murine retinal ganglion cells (RGCs) can be augmented by both visual stimulation and chemogenetics, or, more potently, by combining both methods. The potential for stimulating such axon regeneration has implications not only for ocular disorders, such as glaucoma, but also for other CNS disorders in which nerve regeneration is required.
The inability of crushed optic nerve to regenerate spontaneously has been established through multiple scientific reports and is often employed in basic glaucoma and other ocular research modelling. According to the researchers, regenerative failure following optic crush is consistent with hundreds of reports spanning many decades. However, electrical stimulation of retinal ganglion cells (RGCs) has been shown to provide some accelerated outgrowth of injured axons and such an observation motivated the current researchers to use visual stimulus to drive electrical activity in mature RGCs. High contrast visual stimulation daily for 3 weeks following optic nerve crush showed some degree of RGC regeneration. When such a stimulus is combined with a strategy to augment intrinsic cell growth-promoting factors, including mammalian target of rapamycIn (MTOR), in addition to removing visual input for the contralateral eye, a synergistic effect occurs which facilitates the long distance regeneration of RGCs, down the full length of the optic nerve and into the optic chiasma in the brain. Moreover, labeling of new out-growths show a capability of the nerves to correctly target the correct specific regions of the forebrain and mid-brain demonstrating a remarkable plasticity of CNS neurons previously considered beyond rescue.
According to the authors, the research indicates that “under the appropriate conditions, mature RGCs are capable of regrowing axons into the brain and forming connections with appropriate target neurons. This regeneration leads to partial recovery of several visual functions, suggesting that some degree of functional synapse re-formation can take place in the adult visual pathway”. Commenting on the research milestone, funded by the National Eye Institute (NEI), Paul A. Sieving, MD, PhD, and director of the NEI stated, “reconnecting neurons in the visual system is one of the biggest challenges to developing regenerative therapies for blinding eye diseases like glaucoma. This research shows that mammals have a greater capacity for central nervous system regeneration than previously known.” In addition, the ability to direct long-distance axon regeneration may also hold implications for the development of treatments for damaged spinal cord and other CNS regions.