The findings on retina self-repair in mammals will be published this week in the Early Edition of the Proceedings of the National Academy of Sciences. Other scientists have shown before that certain retina nerve cells from mice can proliferate in a laboratory dish. Today's report gives evidence that retina cells can be encouraged to regenerate in living mice.
The UW researchers in the laboratory of Dr. Tom Reh, professor of biological structure, studied a particular retinal cell called the Müller glia.
"This type of cell exists in all the retinas of all vertebrates," Reh said, "so the cellular source for regeneration is present in the human retina." He added that further studies of the potential of these cells to regenerate and of methods to re-generate them may lead to new treatments for vision loss from retina-damaging diseases, like macular degeneration.
The researchers pointed out the remarkable ability of cold-blooded vertebrates like fish to regenerate their retinas after damage. Birds, which are warm-blooded, have some limited ability to regenerate retinal nerve cells after exposure to nerve toxins. Fish can generate all types of retinal nerve cells, the researcher said, but chicks produce only a few types of retinal nerve cell replacements, and few, if any, receptors for detecting light.
Müller glia cells generally stop dividing after a baby's eyes pass a certain developmental stage. In both fish and birds, the researchers explained, damage to retinal cells prompts the specialized Müller glia cells to start dividing again and to increase their options by becoming a more general type of cell called a progenitor cell. These progenitor cells can then turn into any of several types of specialized nerve cells.
Compared to birds, the scientist said, mammals have an even more limited Müller glia cell response to injury. In an injured mouse or rat retina, the cells may react and become larger, but few start dividing again.
Because the Müller glia cells appeared to have the potential to regrow but won't do so spontaneously after an injury, several groups of researchers have tried to stimulate them to grow in lab dishes and in lab animals by injecting cell growth factors or factors that re-activate certain genes that were silenced after embryonic development. These studies showed that the Müller glia cells could be artificially stimulated to start dividing again, and some began to show light-detecting receptors. However, these studies, the researchers noted, weren't able to detect any regenerated inner retina nerve cells, except when the Müller glia cells were genetically modified with genes that specifically promote the formation of amacrine cells, which act as intermediaries in transmitting nerve signals.
"This was puzzling," Reh said, "because in chicks amacrine cells are the primary retinal cells that are regenerated after injury." To resolve the discrepancy between what was detected in chicks and not detected in rodents, the Reh laboratory conducted a systematic analysis of the response to injury in the mouse retina, and the effects of specific growth factor stimulation on the proliferation of Müller glia cells.
The researchers injected a substance into the retina to eliminate ganglion cells (a type of nerve cell found near the surface of the retina) and amacrine cells. Then by injecting the eye with epidermal growth factor (EGF), fibroblast growth factor 1 (FGF1) or a combination of FGF1 and insulin, they were able to stimulate the Müller glia cells to re-start their dividing engines and begin to proliferate across the retina.
The proliferating Müller glia cells first transformed into unspecialized cells. The researchers were able to detect this transformation by checking for chemical markers that indicate progenitor cells. Soon some of these general cells changed into amacrine cells. The researchers detected their presence by checking for chemicals produced only by amacrine cells.
Many of the progenitor cells arising from the dividing Müller glia cells, the researchers observed, died within the first week after their production. However, those that managed to turn into amacrine cells survived for at least 30 days.
"It's not clear why this occurs," the researchers wrote, "but some speculate that nerve cells have to make stable connections with other cells to survive."
In addition to Reh, the authors of the research findings, "Stimulation of Neural Regeneration in the Mouse Retina," were Mike O. Karl, Susan Hayes, Branden Nelson, Kristine Tan, and Brian Buckingham, all of the UW Department of Biological Structure. The research was supported by postdoctoral fellowships from the German Research Foundation, ProRetina Travel Grants, National Research Service Awards, and a National Eye Institute grant from the National Institutes of Health.
Leila Gray | Newswise Science News
World’s Largest Study on Allergic Rhinitis Reveals new Risk Genes
17.07.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Plant mothers talk to their embryos via the hormone auxin
17.07.2018 | Institute of Science and Technology Austria
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
17.07.2018 | Power and Electrical Engineering
17.07.2018 | Life Sciences
16.07.2018 | Physics and Astronomy