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Embryonic retinal cells and support to mature retinal neurons.

ABSTRACT: Purpose. There is a paucity of neuron replacement studies for retinal ganglion cells. Given the complex phenotype of these neurons, replacement of ganglion cells may be impossible. However, transplanted embryonic cells could provide factors that promote the survival of these neurons. The authors sought to determine whether transplanted embryonic retinal cells from various stages of development influence the survival of mature ganglion cells Methods. Acutely dissociated retinal cells, obtained from chick embryos, were transplanted into the vitreous chamber of posthatch chicken eyes after the ganglion cells were selectively damaged. Eight days after transplantation, numbers of ganglion cells were determined Results. Embryonic retinal cells from embryonic day (E)7, E10, and E11 promoted the survival of ganglion cells, whereas cells from earlier or later stages of development or from other tissue sources did not. The environment provided by the posthatch eye did not support the proliferation of the embryo-derived cells, unlike the environment provided by culture conditions. Furthermore, cells that migrated into the retina failed to express neuronal or glial markers; those that remained in the vitreous formed aggregates of neuronal and glial cells Conclusions. The environment provided within the mature retina does not support the differentiation and proliferation of retinal progenitors. Furthermore, embryo-derived cells likely produce secreted factors that promote the survival of damaged ganglion cells. Therefore, embryonic retinal cells could be applied as a cell-based survival therapy to treat neurodegenerative diseases of the retina.

SUBMITTER: Stanke JJ

PROVIDER: S-EPMC2868403 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Embryonic retinal cells and support to mature retinal neurons.

Stanke Jennifer J JJ Fischer Andy J AJ

Investigative ophthalmology & visual science 20091105 4

Purpose. There is a paucity of neuron replacement studies for retinal ganglion cells. Given the complex phenotype of these neurons, replacement of ganglion cells may be impossible. However, transplanted embryonic cells could provide factors that promote the survival of these neurons. The authors sought to determine whether transplanted embryonic retinal cells from various stages of development influence the survival of mature ganglion cells Methods. Acutely dissociated retinal cells, obtained fr ...[more]

PMID: 19892872

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Project description:IntroductionVitamin B3 has been shown to play an important role during embryogenesis. Specifically, there is growing evidence that nicotinamide, the biologically active form of vitamin B3, plays a critical role as a morphogen in the differentiation of stem cells to mature cell phenotypes, including those of the central nervous system (CNS). Detailed knowledge of the action of small molecules during neuronal differentiation is not only critical for uncovering mechanisms underlying lineage-specification, but also to establish more effective differentiation protocols to obtain clinically relevant cells for regenerative therapies for neurodegenerative conditions such as Huntington's disease (HD). Thus, this study aimed to investigate the potential of nicotinamide to promote the conversion of stem cells to mature CNS neurons.MethodsNicotinamide was applied to differentiating mouse embryonic stem cells (mESC; Sox1GFP knock-in 46C cell line) during their conversion towards a neural fate. Cells were assessed for changes in their proliferation, differentiation and maturation; using immunocytochemistry and morphometric analysis methods.ResultsResults presented indicate that 10 mM nicotinamide, when added at the initial stages of differentiation, promoted accelerated progression of ESCs to a neural lineage in adherent monolayer cultures. By 14 days in vitro (DIV), early exposure to nicotinamide was shown to increase the numbers of differentiated βIII-tubulin-positive neurons. Nicotinamide decreased the proportion of pluripotent stem cells, concomitantly increasing numbers of neural progenitors at 4 DIV. These progenitors then underwent rapid conversion to neurons, observed by a reduction in Sox 1 expression and decreased numbers of neural progenitors in the cultures at 14 DIV. Furthermore, GABAergic neurons generated in the presence of nicotinamide showed increased maturity and complexity of neurites at 14 DIV. Therefore, addition of nicotinamide alone caused an accelerated passage of pluripotent cells through lineage specification and further to non-dividing mature neurons.ConclusionsOur results show that, within an optimal dose range, nicotinamide is able to singly and selectively direct the conversion of embryonic stem cells to mature neurons, and therefore may be a critical factor for normal brain development, thus supporting previous evidence of the fundamental role of vitamins and their metabolites during early CNS development. In addition, nicotinamide may offer a simple effective supplement to enhance the conversion of stem cells to clinically relevant neurons.

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Embryonic retinal cells and support to mature retinal neurons.

Publications

Embryonic retinal cells and support to mature retinal neurons.

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