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J. J. Stanke, A. J. Fischer; The Neuroprotective Effects of Transplanted Embryo-Derived Retinal Cells Are Developmental Stage Specific. Invest. Ophthalmol. Vis. Sci. 2009;50(13):125.
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Efforts to replace retinal neurons lost to disease or injury has included the development of techniques to transplant progenitors. Neuron replacement has met with relatively little success. However, increases in retinal function from enhanced survival of host neurons has been suggested in some transplantation studies. Thus, transplantation of retinal progenitors may have the benefit of rescuing retinal neurons. The purpose of this study is to determine the developmental stage at which embryo-derived retinal cells promote ganglion cell survival to the greatest extent.
Colchicine was delivered bilaterally to post-hatch day two (P2) chicks to induce the death of ganglion cells (GCs). Two days after injury, tectal, wing bud or retinal cells from GFP-transgenic embryos were transplanted into one eye. Eight days later, retinae were labeled for the ganglion cell specific pou-domain transcription factor, Brn-3a. Numbers of GCs were counted from the central, dorsal, beakal, and temporal areas of the retina. Aggregates of transplanted embryo-derived cells that failed to migrate into the retina were sectioned and immunolabeled with a variety of cell-type distinguishing markers. In addition, we determined numbers of proliferating cells using BrdU-labeling to assess whether rates of proliferation differed between cells that were transplanted or maintained in vitro.
We found that retinal cells from E10 effectively supported the survival of GCs. Embryo-derived tectal, wing bud and retinal cells from earlier stages of development had a lesser effect on the survival of GCs. Transplanted embryonic retinal progenitors ceased to proliferate, whereas cells maintained in culture continued to divide. Transplanted cells that remained in the vitreous and cultured cells differentiated into all types of retinal cells, whereas cells that migrated into the retina failed to differentiate as neurons.
We conclude that (1) E10 retinal cells promote the survival of GCs, (2) embryo-derived cells that migrate into the mature retina fail to differentiate, and (3) the environment provided by the post-hatch eye does not support the proliferation of embryonic retinal progenitors.
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