May 2003
Volume 44, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2003
Embryonic Stem Cell Derived Neural Precursors Transplanted into Mouse Models of Retinal Degeneration
Author Affiliations & Notes
  • M.L. Katz
    Mason Eye Institute, Univ of MO, Columbia, MO, United States
  • J.S. Meyer
    Division of Biological Sciences, Univ of MO, Columbia, MO, United States
  • J.A. Maruniak
    Division of Biological Sciences, Univ of MO, Columbia, MO, United States
  • M.D. Kirk
    Division of Biological Sciences, Univ of MO, Columbia, MO, United States
  • Footnotes
    Commercial Relationships  M.L. Katz, None; J.S. Meyer, None; J.A. Maruniak, None; M.D. Kirk, None.
  • Footnotes
    Support  NIH grant NS38987, Children's Brain Diseases Foundation, Batten Disease Research & Support Associati
Investigative Ophthalmology & Visual Science May 2003, Vol.44, 1678. doi:
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      M.L. Katz, J.S. Meyer, J.A. Maruniak, M.D. Kirk; Embryonic Stem Cell Derived Neural Precursors Transplanted into Mouse Models of Retinal Degeneration . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1678.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: There are a number of inherited retinal and retinal-neuronal degenerative diseases, such as retinitis pigmentosa and ceroid-lipofuscinosis, that result in blindness. To date, no effective therapies have been developed to prevent or reverse the degenerative processes in these disorders. Studies were undertaken to evaluate the prospects of using stem cell transplantation as a means of treating these disorders. Methods: Mice with early onset and rapid retinal degeneration (rd1 mutant mice) and with slowly progressive retinal degeneration (mnd mice) were employed for transplantation studies. Mouse embryonic stem (ES) cells expressing enhanced green fluorescent protein (EGFP) were neuralized in vitro and then transplanted into the vitreous of the eyes of 6 week old mice of both strains. At 4 days to 16 weeks after transplantation, the eyes were examined to determine the fate of the transplanted cells. Results: At four days after transplantation, the cells were primarily either in large aggregates in the vitreous, or in close proximity to the inner retinal surface. Some smaller aggregates of just a few transplanted cells and even individual isolated cells were also observed at this time point. At 6 weeks after transplantation, most of the transplanted cells were spread over the inner retinal surface in a thin sheet. In the rd1 mice, a small fraction of the transplanted cells had integrated into the neural retina, but only as far as the inner plexiform layer. In the mnd mice, there appeared to be more migration of the transplanted cells into the retina, and transplanted cells were observed in all retinal layers. In both mouse strains, most of the transplanted cells expressed general neural markers. Many of the transplanted cells displayed neural-like or even retinal-like morphologies, including extensive neurite-like process outgrowth and formation of varicosities. In addition, many of the transplanted cells displayed general neural markers. Conclusions: ES cells that have been neuralized in vitro associate closely with and even integrate into host retinas that are either at the end stage of degeneration or are actively degenerating. The transplanted cells survive long term in association with the retina without any apparent disruption of retinal morphology. These findings suggest that stem cells may be an important tool for developing therapies for retinal and neuronal degenerative disorders.

Keywords: retinal degenerations: hereditary • transplantation • regeneration 
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