May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
An Efficient Gene Transferring Vector For Retinal Pigment Epithelium Cells
Author Affiliations & Notes
  • L.–Y. Cheng
    Department of Ophthalmology, Shiley Eye Center UCSD, La Jolla, CA
  • M. Toyoguchi
    Department of Ophthalmology, Shiley Eye Center UCSD, La Jolla, CA
  • D.J. Looney
    Department of Medicine, VA Medical Center and UCSD, La Jolla, CA
  • J. Lee
    Department of Ophthalmology, Shiley Eye Center UCSD, La Jolla, CA
  • H.J. Koh
    Department of Ophthalmology, Shiley Eye Center UCSD, La Jolla, CA
  • M.C. Davidson
    Department of Ophthalmology, Shiley Eye Center UCSD, La Jolla, CA
  • W.R. Freeman
    Department of Ophthalmology, Shiley Eye Center UCSD, La Jolla, CA
  • Footnotes
    Commercial Relationships  L. Cheng, None; M. Toyoguchi, None; D.J. Looney, None; J. Lee, None; H.J. Koh, None; M.C. Davidson, None; W.R. Freeman, None.
  • Footnotes
    Support  NIH EY 07366 and a gift from Vision of Children Foundation, San Diego, CA
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 3704. doi:
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      L.–Y. Cheng, M. Toyoguchi, D.J. Looney, J. Lee, H.J. Koh, M.C. Davidson, W.R. Freeman; An Efficient Gene Transferring Vector For Retinal Pigment Epithelium Cells . Invest. Ophthalmol. Vis. Sci. 2004;45(13):3704.

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

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Abstract

Abstract: : Purpose: To evaluate the safety and efficiency of an improved FIV viral vector for gene delivery into the mammalian retina. Methods: A second generation FIV vector was constructed by deleting the putative packaging signal and introducing posttranscriptional regulatory element to a first generation FIV vector. The improved FIV vector was administered into eight rabbit eyes (40µl) and thirteen rat eyes (5µl) at the same concentration of 1.5x107 transducing units. After vector administration, the eyes were monitored using slit–lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, and ERG. After sacrificing the animal, the eye tissues were processed for light and electron microscopy as well as immunohistochemistry. Results: The second generation FIV vectors caused transient rabbit vitritis and/or papilitis without other abnormalities during a 6–month observation period. Tropism of the vectors in the rabbit eye included retinal pigmemt epithelium (RPE) cells and ganglion cells. The RPE cell was the dominant cell type transduced and transduction was contained at the retinal bleb area with a 90% transduction rate. Administration of the second generation FIV vector into rat eyes did not demonstrate any toxicity over a 24–month follow–up. Tropism in the rat eye included the RPE and ganglion cells. The RPE transduction rate in the rat eye was 50%. Transgene expression was persistent in both species over the experimental time. Conclusions: The second generation FIV vector appears to be a very efficient vector for carrying therapeutic genes into RPE cells, which could be very useful in treating certain retinal diseases.

Keywords: retina • gene/expression • retinal pigment epithelium 
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