May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Hematopoietic Stem Cells Differentiate Into Retinal Pigment Epithelium Cells Following Sodium Iodate Injury
Author Affiliations & Notes
  • N. Sengupta
    Pharmacology/Therapeutics,
    University of Florida, Gainesville, FL
  • S. Caballero
    Pharmacology/Therapeutics,
    University of Florida, Gainesville, FL
  • S.M. Sullivan
    Pharmaceutics,
    University of Florida, Gainesville, FL
  • W.W. Hauswirth
    Ophthalmology,
    University of Florida, Gainesville, FL
  • S. Kaushal
    Ophthalmology,
    University of Florida, Gainesville, FL
  • J.–X. Ma
    Medicine, Oklahoma University, Oklahoma City, OK
  • M.B. Grant
    Pharmacology/Therapeutics,
    University of Florida, Gainesville, FL
  • Footnotes
    Commercial Relationships  N. Sengupta, None; S. Caballero, None; S.M. Sullivan, None; W.W. Hauswirth, None; S. Kaushal, None; J. Ma, None; M.B. Grant, None.
  • Footnotes
    Support  JDRF 4–2000–847 and NIH Grants EY007739, EY012601, EY014818
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 3252. doi:
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      N. Sengupta, S. Caballero, S.M. Sullivan, W.W. Hauswirth, S. Kaushal, J.–X. Ma, M.B. Grant; Hematopoietic Stem Cells Differentiate Into Retinal Pigment Epithelium Cells Following Sodium Iodate Injury . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3252.

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

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Abstract

Abstract: : Purpose: Hematopoietic stem cells (HSC) or their progeny, endothelial precursor cells, have been shown to have marked plasticity and be involved in repair. It has been documented that embryonic stem cells can be forced to differentiate into specific cell types by infecting the cells with viral vectors expressing terminal differentiation markers. We asked if HSC can home to sites of retinal pigment epithelium (RPE) cell injury and become RPE when transduced to express an RPE–specific protein. Methods: The RPE of C57Bl6 mice was selectively injured by either systemic or intravitreal injection of sodium iodate. Enriched HSC from bone marrow of homozygous gfp transgenic mice were infected ex vivo with lentivirus vector expressing either LacZ (sham) or the RPE–specific RPE65 gene. These transduced gfp+ HSC were then injected systemically into the sodium iodate–treated C57Bl6 mice. Additional animals received gfp+ HSC that had not been infected. A final group of animals received a comparable volume of saline by the same administration route as the HSC. Immunohistochemistry and histology were employed to determine the degree of RPE damage and repair, as well as the presence and location of gfp+ cells, endothelial cells, and RPE65 protein. Results: As expected, no cells expressing gfp were seen in mice that did not receive HSC. Sodium iodate injection resulted in major damage to the RPE, to an extent that was not completely rescued by HSC cells expressing RPE65. On flatmounts of the posterior cup the choriocapillaris was visible in areas of RPE loss. Some gfp+ endothelial cells incorporated in these areas. In many damaged areas that showed recovery, gfp+ RPE65–expressing cells were abundant. These gfp+ cells displayed typical RPE morphology. Conclusions: Cells that co–expressed gfp and RPE65 were present in areas of RPE ablation. This supports that HSC are capable of differentiating into RPE cells following injury. The overexpression of RPE65 is apparently sufficient to drive the differentiation of HSC to RPE. No gfp+ endothelial cells also expressed RPE65. These findings suggest the possibility that a patient's own HSC could be modified ex vivo to induce specific differentiation, and then returned to the patient to replace lost or damaged RPE.

Keywords: retinal degenerations: cell biology • pathology: experimental • gene transfer/gene therapy 
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