Abstract
Vision is by far the most dominant and important sense to people, with 80% or more of all sensory information being perceived by means of sight. At present, there are no adequate treatments available to restore vision after photoreceptor cell death or/and optic nerve degeneration caused by trauma or degeneration. Restoring vision is an urgent and unmet medical need. With current advances in genetic testing, ocular imaging, in vivo modeling, innovative surgical approaches, and ocular therapeutics (stem cell and gene therapies, small molecules, in vivo DNA engineering, antibodies and immunomodulatory compounds, and biomaterials) major advances have been realized for ameliorating the devastating impact of blindness. Addressing corneal blindness and cataracts became feasible due to truly innovative limbal stem cell therapies, artificial cornea work, microsurgical techniques, and materials for lens/cornea replacement. Likewise, the path for delaying vision loss in conditions such as dry and wet Age-related macular degeneration, as well as diabetic retinopathy, is becoming better understood due to innovative cell and gene therapy treatments, anti-vascular endothelial growth factor antibody therapies, and immunomodulatory therapies.
Nevertheless, restoring the neural components of the visual system, such as photoreceptors and retinal ganglion cells forming the optic nerve, in cases of advanced degeneration remains the most difficult task because of the need to restore not only the cell presence but also the connectivity that enables neural retina to carry out visual function. New out-of-the-box treatment modalities need to be developed, which draw knowledge from understanding stemness and regeneration of mammalian neural tissue and epigenetic blocks preventing regeneration of retina/optic nerve in the human eye. The examples from lower species regenerating the neural component of their visual system are available and informative for teaching us how we can restore retina and optic nerve after major trauma or in advanced degeneration. These possibilities are gradually becoming a reality. Combining expertise from different fields will be critical for creating novel regenerative medicine approaches to reverse vision loss.
Regeneration and transplantation are 2 approaches with the potential to revert vision loss in cases of profound and even terminal blindness. All other approaches, including gene therapy, are based on ameliorating or slowing down vision loss; however, they depend on the existence of salvageable ocular structures, for example, retina, cornea, and optic nerve, and do not attempt to rebuild tissues de novo. Compared with regeneration, stem cell therapy stands out as a lower hanging fruit, because it is more understood and technically the most feasible. The eye is a small encapsulated organ, with relatively simple neuroanatomy and immune privilege. Ocular space is easily accessible for transplantation and retinal grafts can be easily visualized using noninvasive methods, such as those described in the accompanying articles. Transplantation of retinal pigment epithelium is leading the way for other retinal therapies and is facilitated by no need for developing synaptic connectivity, in contrast to transplantation of neuronal elements. Retinal organoid technologies provide a replenishable source of human retina and photoreceptors to develop next-level technologies for rebuilding the most complex component of our visual system—the neural retina.
Multidiscipline meetings of experts, such as the Disruptive Technologies session that took place during the 2019 Association for Ocular Pharmacology and Therapeutics conference in New Orleans, are needed to promote cross-pollination and expertise sharing for developing new treatment modalities. The reports from the meeting are refreshing and provide real hope that new vision restoration therapies are coming soon to millions of those who need them.