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N. Cuenca, G.C. Martínez–Navarrete, A. Angulo, J. Martín–Nieto; Process of Differentiation of Retinal Neurons from Stem Cells in the Peripheral Retinal Margin of Primates . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5408.
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Purpose:Neurogenesis and regeneration of retinal neurons have not been reported in adult mammals. Yet retinal stem cells and differentiating neurons have been identified in dissociated cell cultures from the ciliary body epithelium of adult rodents. The purpose of this work was the in situ visualization of retinal neurons in the process of differentiation from stem cells in the ciliary body and adjacent, far peripheral retina of adult monkeys and humans. Methods:Cryostat sections of the ciliary body pars plana and retinal peripheral margin from adult macaques and humans were singly and doubly immunostained with specific antibodies against nestin (a neural stem cell marker) and a set of phenotypic protein markers of all mature retinal neuronal types. Cell micrographs were taken under confocal laser–scanning fluorescence microscopy. Results:We have immunohistochemically identified nestin–expressing cells in the pars plana epithelium and far peripheral retina of monkeys and humans. As well, we have visualized morphologically undifferentiated neurons in the far peripheral retina. A gradient of maturation from undifferentiated cells to fully–developed neurons (especially photoreceptors and rod bipolar cells) was found when advancing from the ora serrata to the peripheral laminated retina. In addition to sequential morphological development and expression of specific markers of mature retinal neurons, establishment of correct synaptic contacts was visualized along this gradient. Conclusions:The peripheral retinal margin constitutes a region where differentiation of all retinal neuronal types from stem cells takes place in adult human and non–human primates. This process can be postulated to have a role in the turnover of retinal neurons during the life span of mammals.
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