December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Recombinant Adeno-Associated Virus (rAAV) Is Able to Transduce Retinal Muller Cells
Author Affiliations & Notes
  • F-Q Liang
    Dept of Ophthalmology Univ of Pennsylvania Philadelphia PA
  • E Surace
    Dept of Ophthalmology Univ of Pennsylvania Philadelphia PA
  • N Dejneka
    Dept of Ophthalmology Univ of Pennsylvania Philadelphia PA
  • J Bennett
    Dept of Ophthalmology Univ of Pennsylvania Philadelphia PA
  • Footnotes
    Commercial Relationships   F. Liang, None; E. Surace, None; N. Dejneka, None; J. Bennett, None. Grant Identification: NIH F3207073, RO1 EY 10820, FFB, RPB, P. and E. Mackall Trust, and the F.M. Kirby Foundation
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 4613. doi:
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    • Get Citation

      F-Q Liang, E Surace, N Dejneka, J Bennett; Recombinant Adeno-Associated Virus (rAAV) Is Able to Transduce Retinal Muller Cells . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4613.

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Abstract

Abstract: : Purpose: Although rAAV primarily targets retinal neurons, recent studies have demonstrated that rAAV can transduce some Muller cells in mutant rhodopsin transgenic rats (Liang et al. Mol. Ther. 4:461-472, 2001). The purpose of this study aimed to determine (1) whether rAAV efficiently transduce Muller cells, both in vitro and in vivo; and (2) whether Muller cells express AAV receptors. Method: rAAV.GFP encoded the EGFP cDNA under the regulation of a CMV promoter. This vector was administered intravitreally to 1-month old wild-type rats and mice as well as retinal degenerative mice (rds/rds). Animals were sacrificed 2 months post-injection. To see whether adenovirus (Ad) was able to accelerate AAV-mediated transgene expression, some wild-type mice received intravitreal injections of a mixture of rAAV.GFP and wild-type Ad and were sacrificed 2 days later. Eyes were processed and examined histologically for GFP expression. GFP fluorescence was also examined in rMc-1 cells (a rat Muller cell line provided by V. Sathy at Northwestern Univ.) 12-72 hours following rAAV.GFP infection. AAV receptor expression was studied in both retinal sections and rMc-1 cells using antibodies directed against fibroblast growth factor receptor 1 (FGFR-1) and heparan sulfate glycoprotein (HSGP). Results: Intravitreal injection of rAAV.GFP resulted in strong GFP expression in Müller and ganglion cells. The ability of rAAV to target Muller cells was confirmed by its efficient transduction of rMc-1 cells in vitro and by the expression of FGFR-1 and HSGP receptors. Intravitreal injection of a mixture of rAAV and Ad led to exclusive and early expression of GFP in the Muller cells, suggesting that Muller cells are able to uptake both rAAV and Ad. Conclusion: Our study demonstrated that Muller cells express AAV receptors and can be efficiently transduced by rAAV after intravitreal injection. Given the easy accessibility of these cells from the vitreous base and their role in mediating photoreceptor protection, Muller cells may serve as a useful target for gene transfer of trophic factors by rAAV in the treatment of degenerative retinal diseases.

Keywords: 419 gene transfer/gene therapy • 479 Muller cells • 565 retinal glia 
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