Rods, cones and nerve layers in the retina. The front (anterior) of the eye is on the left. Light (from the left) passes through several transparent nerve layers to reach the rods and cones (far right). A chemical change in the rods and cones send a signal back to the nerves. The signal goes first to the bipolar and horizontal cells (yellow layer), then to the amacrine cells and ganglion cells (purple layer), then to the optic nerve fibres. The signals are processed in these layers. First, the signals start as raw outputs of points in the rod and cone cells. Then the nerve layers identify simple shapes, such as bright points surrounded by dark points, edges, and movement. (Based on a drawing by Ramón y Cajal.)
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. Glaucoma and other optic neuropathies cause vision loss through the permanent destruction of RGCs. In humans, RGCs are incapable of regenerating on their own. There are 2 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 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. https://nei.nih.gov/news/briefs/helping-retina-regenerate
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