A new report from the National Eye Institute’s (NEI) Audacious Goals Initiative (AGI) outlines 2 possible therapeutic strategies to create new neurons in the retina.
“Replacing retinal ganglion cells (RGCs) is a major challenge for the AGI,” said Steven Becker, PhD, who coordinates the cross-disciplinary research initiative to restore vision by regenerating neurons and their connections in the eye.
The report, published in Translational Vision Science and Technology, was authored by Monica Vetter, PhD, University of Utah, and Peter Hitchcock, PhD, University of Michigan.
Strategies for Generating Transplantable RGCs
The first approach discusses growing new RGCs from stem cells and transplanting them into a patient’s retina. While preclinical testing has shown promise, challenges to this approach include producing adequate quantities for therapy and long-term storage of these sensitive cells. In addition, scientists have yet to determine the optimal stage of cellular development for transplantation, as cells that are too naïve may develop into unintended cell types, while those that are more mature might not easily integrate into the retina.
Potential Endogenous Cellular Sources for RGC Regeneration
The second approach focuses on recruiting other retinal cell types to reprogram into RGCs in vivo. Understanding the cues that direct RGC maturation and integration with other cells is the key to this process, which occurs naturally in some organisms. An example of this is found in zebrafish, which can induce Müller glia to convert into new RGCs in response to cell death from injury. Other cell types that may hold potential for reprogramming include retinal pigment epithelial cells, ciliary epithelial cells, amacrine cells, and astrocytes.
The report also addresses the gaps in scientific knowledge and barriers to progress that slow such research, including a lack of understanding of the genetic factors and signaling pathways that promote endogenous cell reprogramming. Finally, the authors assert the need for standardized criteria to evaluate RGCs and better assessment of which imaging techniques are best to examine RGC integration in the retina.