Many causes of blindness involve the loss of retinal neurons. In birds and fish, a cell called the Muller glial cell can serve as a stem cell to regenerate the lost cells. Unfortunately mammals – including mice and humans -- do not normally regenerate new retinal cells after loss or injury, resulting in permanent blindness.
In a recent report published in Nature, Adjunct Professors of Ophthalmology Tom Reh, PhD, Rachel Wong, PhD, and Fred Rieke, PhD demonstrated for the first time that functional neurons can be regenerated in the mammalian retina from Muller glial cells. After a study conducted by Dr. Dan Goldman from University of Michigan found that a particular gene, Ascl1, was turned on in the glial cells of fish and led to regeneration, Reh’s laboratory along with collaborators from the Rieke and Wong labs, devised a way to artificially turn on this same gene in the Müller glia of mice. This was done using transgenic techniques as well as with a small molecule called TSA to modify the histone genes of chromatin to promote expression.
“Since the Müller glia can survive long after neurons are gone, our ultimate hope is that we can simulate the Müller glia with Ascl1 and TSA to replace these lost neurons,” notes Reh. His group found that regenerated neurons connected with those that survived the injury, and also responded to light. “If we can make the Müller glia do the same thing in people, this may well help some patients improve their vision,” says Reh.
In the published study, most of the newly created retinal neurons were ‘interneurons’, cells that communicate between the photoreceptors and retinal nerve cells. Further research is underway in both Reh and Wong labs to coax Muller cells to become other specific cells (either photoreceptor or ganglion cells). The groups are also working on a way to deliver the Ascl1 to the Müller glia via a therapeutic virus, similar to that used for other types of ocular gene therapy.
More information about this study can be found in the August 3, 2017 issue of Nature.
Jorstad, N. L., Wilken, M. S., Grimes, W. N., Wohl, S. G., VandenBosch, L. S., Yoshimatsu, T., Reh, T. A. (2017, August 3). Stimulation of functional neuronal regeneration from Müller glia in adult mice. Nature, 548, 103-107.
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