Research into Retinal Regeneration

Our lab is also studying the molecular and cellular changes that occur during regeneration of the retina. Click on any of the highlighted links to find out more about retinal regeneration in various species. Many of our earlier studies explored the mechanisms of retinal regeneration in amphibians . In some urodeles and larval anurans the retina can regenerate through a process known as "transdifferentiation" of the retinal pigmented epithelium (RPE). For a review of this area of research see Levine and Reh (1998). In the fish, retinal regeneration is also possible in adult animals, but the new cells are thought to arise by a very different mechanism. There are at least two possible sources of regeneration in the fish; it is thought that either specialized resident progenitor cells, the rod precursors, become multipotent retinal progenitors and replace all classes of retinal neurons after retinal damage. However, more recently it has been reported that there are a small number of retinal stem cells within the neural retina of the fish, and that these are re-activated after retinal damage. Lastly, Raymond and Hitchcock have proposed that Muller glial cells might also contribute to the regeneration observed in the fish retina.

The two very different cellular mechanisms for retinal regeneration in fish and amphibians are well established.

Does retinal regeneration occur in higher vertebrates, like birds or mammals? What about retinal regeneration in people? At this time, there have been no reports of retinal regeneration in any mammals, like ourselves.   However, research into the basic mechanisms of retinal regeneration in other species may help to understand why it fails to occur in mammals.

However, it has been known for over thirty years that embryonic chick retina can regenerate from the RPE, by a process very similar to that which occurs in the amphibian-transdifferentiation of the RPE layer. Unfortunately, the capacity of the RPE to transdifferentiate into neural retina is lost very early in development (see Pittack and Reh, 1995 for example).

Several years ago we found that the bird retina has a limited capacity to regenerate new neurons after the retina is experimentally damaged with neurotoxins. We have found that the Muller glial cells re-enter mitosis and some of their progeny differentiate into new retinal neurons ( Fischer, A.J. and Reh, TA (2001) Muller glia are a potential source of neural regeneration in the postnatal chicken retina. Nature Neuroscience 4:247-252 ). We are currently working to understand how to stimulate the process of retinal regeneration in birds, since at present relatively few of the newly generated cells develop as neurons. In addition, we are working to understand why the process of retinal regeneration fails in mammals.

 

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