IOVS Archives of Disease in Childhood
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(Investigative Ophthalmology and Visual Science. 2006;47:745-752.)
© 2006 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.05-0398
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Recombinant AAV-Transduced Iris Pigment Epithelial Cell Transplantation May Transfer Vector to Native RPE but Suppress Systemic Dissemination

Yuki Yoshioka,1 Toshiaki Abe,2 Ryosuke Wakusawa,1 Takuya Moriya,3 Shizue Mochizuki,3 Yoko Saigo,1 Takae Saito,1 Hiromi Murata,1 Yumi Tokita,2 Takashi Iseya,1 Eriko Sugano,1 Hiroshi Tomita,1 Yoshiko Sagara,1 and Makoto Tamai1

1From the Department of Ophthalmology and Visual Science, the 2Division of Clinical Cell Therapy, and the 3Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.

PURPOSE. To determine whether adenoassociated virus (AAV) vectors transduced into iris pigment epithelial (IPE) cells and transplanted into the subretinal space of rats will transfer the AAV genome to the host cells and whether the vectors are disseminated systemically.

METHODS. Recombinant (r)AAV was transduced into rat IPE cells and transplanted into the subretinal space of rats. For the control, rAAVs alone were injected subretinally. The transplanted IPE cells were detected by LacZ staining. Immunohistochemistry, electron microscopy, electroretinography, and fluorescein–dextran angiography were performed. DNA was extracted from various organs and blood and examined for the AAV genome by polymerase chain reaction.

RESULTS. No toxicity from rAAV transduction was observed in vitro. LacZ was expressed in the transplanted cells 1 and 2 weeks after transplantation. At 4 and 12 weeks, fewer transplanted cells were detected than at 1 week, and LacZ expression was occasionally detected at the level of host retinal pigment epithelial (RPE) cells. Expression was also detected in ciliary body epithelial cells. The electroretinograms and fluorescein–dextran angiography were only mildly altered. Significantly lower levels of AAV genome were detected in the organs and blood of rats receiving rAAV-IPE cell transplants than with direct intravenous injection of AAV vectors.

CONCLUSIONS. AAV-mediated LacZ was expressed in the transplanted cells after subretinal transplantation, and the transplanted IPE cells may transfer the rAAV to host tissues, such as RPE cells, long after the transplantation. This method of gene delivery did not lead to systemic dissemination of the vectors.




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T. Abe, R. Wakusawa, H. Seto, N. Asai, T. Saito, and K. Nishida
Topical Doxycycline Can Induce Expression of BDNF in Transduced Retinal Pigment Epithelial Cells Transplanted into the Subretinal Space
Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3631 - 3639.
[Abstract] [Full Text] [PDF]


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