Retinal regeneration

Retinal regeneration refers to the restoration of vision in vertebrates that have suffered retinal lesions or retinal degeneration.

The two most well-studied mechanisms of retinal regeneration are cell-mediated regeneration and cellular transplantation. Regenerative processes may have applications in humans for treating degenerative retinal diseases such as retinitis pigmentosa. While mammals such as humans and mice lack the innate ability to regenerate the retina, lower vertebrates such as teleost fish and salamanders are capable of regenerating lost retinal tissue in the event of damage.

Zebrafish, like other teleost fish, possess the innate ability to regenerate retinal damage. This ability combined with the considerable similarity between teleost and mammalian retinal structure makes zebrafish an attractive model for the study of retinal regeneration.Muller glia are a type of glial cell present in both the teleost and mammalian retina. Retinal regeneration in zebrafish is mediated by Muller glia, which dedifferentiate into stem-like cells and proliferate into neural progenitor cells in response to retinal damage. While Muller glia division is responsible for the regeneration of the retina in all cases of retinal damage, the case of photoreceptor loss due to light damage is particularly well characterized. In response to photoreceptor ablation, Muller glia dedifferentiate and undergo a single asymmetric division to produce a neural progenitor cell and a new Muller glia cell. The neural progenitor cell proliferates to form a cluster of neural progenitors, which migrate to the outer nuclear layer of the retina and differentiate into photoreceptors to replace the lost cells. This process restores retinal function to the injured fish. Understanding the underlying mechanisms may provide insight into treatment options for degenerative retinal diseases in mammals.

Several proteins and signaling pathways have been described and characterized in the process of retinal regeneration. The roles of a few important elements are summarized below:

Rod precursor differentiation is another mechanism by which zebrafish can replace lost retinal neurons. Rod precursors are produced during normal zebrafish growth and localize to the outer nuclear layer of the retina. In the event of chronic or small-scale rod photoreceptor death, rod precursors proliferate and differentiate into new rod photoreceptors. This population of progenitor cells can be induced to proliferate by means such as injection of growth hormone or selective rod photoreceptor cell death. However, as this regenerative response is more limited than the Muller glia mediated response, much less is known about its underlying mechanisms.

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