NEI Audacious Goals Initiative report outlines strategies to replace or reprogram neurons in the retina.
A new report gives recommendations for regenerating retinal ganglion cells (RGCs), crucial neurons in the back of the eye that carry visual information to the brain. Authored by Monica Vetter, PhD, University of Utah, and Peter Hitchcock, PhD, University of Michigan, the report stems from a 2016 workshop sponsored by the National Eye Institute (NEI) Audacious Goals Initiative (AGI).

“Replacing RGCs is a major challenge for the AGI,” said Steven Becker, PhD, who coordinates the initiative – a sustained effort by the NEI to catalyze research aimed at restoring vision by regenerating the retina, the light–sensitive tissue in the back of the eye. Glaucoma and other optic neuropathies cause vision loss through the permanent destruction of RGCs. In humans, RGCs are incapable of regenerating on their own.

The report summarized two possible therapeutic strategies for RGC regeneration. The first would use stem cells to grow RGCs. These lab–grown cells would then be transplanted to a patient’s retina. While preclinical testing has shown promise, the report details challenges to this approach. For starters, producing adequate quantities for therapy remains difficult and takes many weeks. And researchers are unsure how best to store RGCs for when patients need them. Another challenge is determining the optimal stage of cellular development for transplantation. Cells that are too naïve may develop into unintended cell types, while those that are more mature might not easily integrate into the retina.

The second approach – the focus of the AGI workshop – is to recruit other cell types in a patient’s retina for reprogramming into RGCs. Amphibians do this naturally in response to RGC death from injury. Similarly, adult zebrafish regenerate RGCs by reprogramming cells in the retina called Müller glia. As outlined in the report, the workshop explored additional cell types for potential reprogramming, including retinal pigment epithelial cells, ciliary epithelial cells, amacrine cells, and astrocytes. According to the report, the key to unlocking these endogenous cell sources for RGC reprogramming is understanding the cues that direct their maturation and integration with other cells.

The report calls for research to better define the genetic factors and signaling pathways that promote endogenous cell reprogramming. Additionally, better characterization of the 30–plus types of RGCs is needed. Other key recommendations in the report include systematic comparisons of animal models that do and do not regenerate RGCs, criteria for evaluating RGCs, and imaging techniques to assess RGC integration in the retina.

The report appeared in the journal Translational Vision Science and Technology.