Researchers from Yale University School of Medicine have found a cell reprogramming technique that turns support cells in the retina into stem cells capable of replacing retinal neurons lost due to eye diseases such as diabetic retinopathy.
The study findings, published in the journal Cell Reports, suggest that a biological process in zebrafish, whereby lost retinal neurons are spontaneously replenished after injury, could be utilised in human cell models to help treat an array of eye diseases.
The retina at the back of the eye contains many types of cell, including retinal neurons that process visual images, and support cells that surround them called glial cells.
Three basic types of glial cell are found in the human retina, astroglia, microglia, and Müller glial (MG) cells. The latter have the capacity to become stem cells (or develop into many different cell types) and turn into new retinal neurons.
Previous research has shown that this ability remains dormant in humans, unless it is switched on through injury. However, in zebrafish, this is not the case.
The zebrafish’s MG cells continuously act as a source of retinal stem cells to make up for a sudden loss of retinal neurons.
The first author of the study, professor Bo Che, and colleagues tried to find a way to activate MG human cells so they behave more like the ones in zebrafish.
They first thought of inducing retinal injury through neurotoxins, but this had resulted in the death of even more neurons in other studies.
The goal was therefore to simulate an injury without inflicting an injury and further damage to an already diseased retina.
To do so, the team focused on activating a signalling pathway turned on by injury, called Wnt signalling, which regulates aspects of a glial cell’s fate.
Upon investigating how to stimulate that pathway, the researchers discovered that inserting genes into adult mouse retinas could reprogram MG cells to activate Wnt signalling and induce their proliferation as new retinal neurons without retinal injury.
By controlling which genes are inserted and deleted, they were also able to either up- or down-regulate Wnt signalling to influence specific desired effects on MG proliferation for making retinal neurons as well as interneurons.
This novel potential therapeutic avenue uncovered by Chen could have many interesting applications to treat different age and chronic disease-related retinal degenerations.

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