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Takae Kiyama, Manu Gupta, Steven Wang; Dynamic Neuronal Regeneration in the Mammalian Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2242.
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© ARVO (1962-2015); The Authors (2016-present)
It is becoming clear that many regions in the mammalian central nervous system retain neurogenic property. In aquatic vertebrates, retinas are neurogenic throughout their life span. In these species new neurons are supplied from the ciliary marginal zone (CMZ). Upon injury, Müller glia in the mature retina proliferate and supply new neurons. The mammalian retina is thought to be non-neurogenic and its potential is not explored. Here, we use several genetic modified mice to explore the neurogenic potential in the putative CMZ.
Retinal ganglion cells (RGCs) are required for formation of retina. RGC shortage results in less cells in retina. To test whether insufficient retinal cell trigger neurogenesis, we examined a series of mouse lines with a spectrum of RGC shortage. Cell proliferation and differentiation were examined.
In the normal retina, expression of proneural marker math5 stops postnatal day (P7). In a math5-null retina lacking 95% of RGCs, we observed stronger math5-activity. The math5 activity in this retina is prolonged to P9. In a retina lacking 99 % of RGCs, more significant prolongation of math5 activity to P24 was observed. To ensure this prolongation was a result of RGC shortage but not lack of math5, we used a mouse line lacking 98% RGC but has an intact copy of math5. Math5 activation was prolonged. Our results show that the young mammalian putative CMZ can be triggered to be neurogenic. This result indicates that young mammalian retina contains a region similar to the aquatic vertebrate. We also found that central retina can proliferate till adulthood.
In the RGC-deficient retina, math5 activity was enhanced and prolonged in the putative CMZ. Also cell proliferation and neurogenesis occurred in this retina. Our results demonstrate that mammalian retina tries to fix itself when deficiency is detected providing hope for exploring treatment for retinal degenerative diseases.
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