The Regeneration of Inner Nerve Cells in a Damaged Mammalian Retina Possible

University of Washington (UW) researchers say that it is possible to stimulate the regeneration of inner nerve cells in a damaged mammalian retina, the area at the back of the eye that receives light and sends the images of what one sees to the brain.

Writing about their findings in the Proceedings of the National Academy of Sciences, the researchers revealed that they studied a particular retinal cell called the Muller glia.

"This type of cell exists in all the retinas of all vertebrates, so the cellular source for regeneration is present in the human retina," said lead researcher Tom Reh, a professor of Biological Structure at the university.

He said that developing certain methods to re-generate such cells might lead to new treatments for vision loss from retina-damaging diseases, like macular degeneration.

The researchers pointed out that cold-blooded vertebrates like fish have a remarkable ability to regenerate their retinas after damage, while Birds that are warm-blooded have some limited ability to regenerate retinal nerve cells after exposure to nerve toxins.

While fish can generate all types of retinal nerve cells, the researcher said, chicks produce only a few types of retinal nerve cell replacements, and few receptors for detecting light.

After a baby's eyes pass a certain developmental stage, Muller glia cells generally stop dividing.

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According to the researchers, damage to retinal cells in both fish and birds prompts the specialized Muller glia cells to start dividing again, and to increase their options by becoming a more general type of cell called a progenitor cell. They say that such progenitor cells can then turn into any of several types of specialized nerve cells.

The researchers say that mammals have an even more limited Muller glia cell response to injury, compared to birds. They suggest that in an injured mouse or rat retina, the cells may react and become larger, but few start dividing again.

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The team points out that several research groups have tried to stimulate the Muller glia cells 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.

Observations made during such studies suggested that the Muller glia cells could be artificially stimulated to start dividing again, and to show light-detecting receptors.

However, all those studies had failed to detect any regenerated inner retina nerve cells, except when the Muller 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, because in chicks amacrine cells are the primary retinal cells that are regenerated after injury," Reh said.

With a view to resolving the discrepancy between what was detected in chicks and not detected in rodents, the researchers carried out a systematic analysis of the response to injury in the mouse retina, and the effects of specific growth factor stimulation on the proliferation of Muller glia cells.

They 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 Muller glia cells to re-start their dividing engines and begin to proliferate across the retina.

The proliferating Muller glia cells first transformed into unspecialised cells, something that the researchers were able to detect by checking for chemical markers that indicate progenitor cells.

Soon some of the general cells changed into amacrine cells, and the researchers detected their presence by checking for chemicals produced only by amacrine cells.

The researchers observed that many of the progenitor cells arising from the dividing Muller glia cells died within the first week after their production, but those that managed to turn into amacrine cells survived for at least 30 days.

"It's not clear why this occurs, but some speculate that nerve cells have to make stable connections with other cells to survive," the researchers wrote.

Source-ANI
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