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If you were a fish and your retina was damaged, it could repair itself and your vision would be restored in a few weeks. Sadly, human eyes don't have this ability — yet.
However, new research into retinal regeneration in zebrafish has identified a signal that appears to trigger the self-repair process. If confirmed by follow-up studies, this discovery raises the possibility human retinas might also be induced to regenerate, naturally repairing damage caused by degenerative retinal diseases and injury. Perhaps even age-related macular degeneration or retinitis pigmentosa.
The research was performed by a team of biologists at Vanderbilt University and is described in a paper titled "Neurotransmitter-Regulated Regeneration in the Zebrafish Retina" published Mar. 9 by the journal Stem Cell Reports.
It turns out the structure of retinas of fish and mammals are basically the same. Although a fish retina is very thin, less than 0.5 millimeters (0.019685 of an inch), it contains three layers of nerve cells: (1) photoreceptors that detect light, (2) horizontal cells that integrate signals from photoreceptors and (3) ganglion cells which receive visual information and route it to the brain. In addition, retina contain a special adult stem cell, Müller glia, spanning all three layers, providing mechanical support and electrical insulation.
Graduate student Mahesh Rao recognised that GABA — a fast-acting neurotransmitter known for inhibiting synapses in the brain — might trigger retinal regeneration. He was inspired by results of a study on the mouse hippocampus which found GABA controlled stem cell activity.
So Rao, working with Patton and research assistant professor Dominic Didiano, designed a series of experiments on zebrafish, an animal model used to study regeneration. The experiments revealed high concentrations of GABA in the retina keep Müller glia quiescent. The glia begin de-differentiating and proliferating when GABA concentrations drop.
They tested their hypothesis in two ways: (1) blinding zebrafish then injecting them with drugs to stimulate GABA and by (2) injecting normal zebrafish with an enzyme lowering levels of GABA in their eyes.
Zebrafish blind easily. Placed in total darkness for several days, then suddenly exposed to very bright light, destroys all their photoreceptors. Due to their robust ability to regenerate, however, their eyes recover in just 28 days.
When newly blinded fish were injected with drugs to keep GABA high — regeneration was suppressed.
When normal fish were injected with an enzyme lowering GABA levels, Müller glia began de-differentiating and proliferating — the first stage in the regeneration process.
The researchers' next step is to determine if GABA not only stimulates Müller glia de-differentiation and proliferation, but also differentiation that produces new photoreceptors and other specialized neurons in the retina. They are pursuing this in both zebrafish and mice with a grant from the National Eye Institute's Audacious Goals Initiative.
The research was funded by National Eye Institute grants R01 EYE024354, R21 EY019759 and P30-EY008126.
Different types of nerve cells in the zebrafish retina overlap.