Efficient Gene Transfer to Retinal Pigment Epithelium Cells with Long-term Expression

Overview

Journal Retina

Date 2005 Feb 4

PMID 15689811

Citations 8

Authors

Lingyun Cheng

Mitsuko Toyoguchi

David J Looney

Jeffery Lee

Marie C Davidson

William R Freeman

Affiliations

Soon will be listed here.

Abstract

Purpose: To evaluate the safety and efficiency of feline immunodeficiency virus (FIV) vectors for gene delivery into the mammalian retina.

Methods: A first-generation FIV vector was constructed and administered into rabbit eyes at two different concentrations by intravitreal or subretinal routes. A second-generation FIV vector was also constructed and administered subretinally into both rabbit and rat eyes at the same concentration. After vector administration, eyes were monitored using slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, and electroretinogram. After the rabbits were killed, eye tissues were processed for light microscopy and immunohistochemical analysis.

Results: Administration of both first- and second-generation FIV vectors produced transient vitritis and/or papillitis in rabbits, without other pathologic abnormalities. Retinal pigment epithelium (RPE) cells were the predominant cell type transduced in rabbit eyes, but ganglion cells and Muller cells were also transduced. Transduction was confined to the retinal bleb area. The second-generation FIV vector transduced RPE cells much more efficiently than the first-generation vector (95% vs. 4.5%, respectively; P = 0.0015) in rabbit eyes. In contrast, no toxicity was evident over a 24- to 25-month follow-up period after injection of the second-generation FIV vector into rat eyes. Tropism in the rat eye was similar, including RPE and ganglion cells, and the RPE transduction rate was also high (50%). Transgene expression was persistent in both species over the duration of the experiment.

Conclusion: Second-generation FIV vectors can efficiently transfer genes into RPE cells with resulting long-term expression, properties potentially valuable to gene therapy approaches to some retinal diseases.

Citing Articles

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