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N. Cuenca, A. Angulo, G. Martínez–Navarrete, J. Martín–Nieto; Neurogenesis of Photoreceptors in the Adult Monkey and Human Retina . Invest. Ophthalmol. Vis. Sci. 2005;46(13):575.
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Purpose: Retinal stem cells and differentiating neurons have been identified in vitro in dissociated cell cultures from the ciliary body epithelium of adult rodents and humans. We have here addressed the possibility of neurogenesis of photoreceptors and other neurons taking place in situ in the retina of adult non–human and human primates. Methods: Cryostat vertical sections including the ciliary body pars plana, retinal margin and peripheral retina were obtained from adult macaques and humans. After single and double immunostaining with specific antibodies against nestin (a neural stem cell marker) and a set of phenotypic markers of all mature retinal neuronal types, micrographs were taken under confocal laser–scanning fluorescence microscopy. Transmission electron microscopy studies were also carried out on ultrathin sections. Results: We have immunohistochemically identified nestin–expressing retinal stem cells, together with a variety of morphologically undifferentiated neurons, in both the pars plana and the far peripheral retina of monkeys and humans. A gradient of differentiation from immature cells into fully–developed neurons was found along the peripheral retinal margin in advancing toward the laminated retina, which was especially evident for photoreceptors and bipolar cells. Along this gradient, the sequential morphological development of cells expressing photoreceptor markers was accompanied by the establishment of synaptic contacts with horizontal and bipolar cells. Presumptive rod– and cone–precursor cells displayed opsin expression throughout the cell, and growth in length of outer segments was paralleled by a restriction of visual pigment localization to this region. Additionally, de novo formation of outer segment disc membranes at the upper portion of incipient ellipsoids was observed to occur in these cells from the fusion of vesicles arising from the Golgi complex. Conclusions: The peripheral retinal margin constitutes a region where neurogenesis of photoreceptors and other retinal cell types takes place in a spatial–temporal fashion in adult primates. This process can be envisioned to have a role in the normal turnover of retinal neurons which become lost along life in mammals.
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