Purpose. The aim of this study was to characterize oligonucleotide- polyethylenimine (ODN/PEI) complex preparation for potential transfection of retinal cells in vitro and in vivo. Methods. The effect of medium preparation [HEPES-buffered saline (HBS), water] on particle size and morphology was evaluated. Cultured Lewis rat retinal Müller glial (RMG) cells were transfected using fluorescein isothiocyanate (FITC)-ODN/PEI complexes specifically directed at transforming growth factor beta (TGFβ)-2. Efficacy of transfection was evaluated using confocal microscopy, and regulation of gene expression was assayed using quantitative real-time RT-PCR and ELISA assay. One, 24, and 72 h after injection of FITC-ODN/PEI complexes into the vitreous of rat eyes, their distribution was analyzed on eye sections. Results. Complexes prepared in HBS were smaller than complexes prepared in pure water and presented a core-shell structure. These particles showed a high cellular internalization efficacy, along with a significant and specific down-regulation of TGFβ-2 expression and production in RMG cells, correlating with specific inhibition of cell growth at 72 h. In vivo, complexes efficiently transfect retinal cells and follow a transretinal migration at 24 h. After 72 h, ODN seems to preferentially target RMG cells without inducing any detectable toxicity. Conclusions. Specific down-regulation of TGFβ-2 expression using ODN/PEI complexes may have potential interest for the treatment of retinal diseases associated with glial proliferation. © 2006 Springer Science + Business Media, Inc.
CITATION STYLE
Gomes Dos Santos, A. L., Bochot, A., Tsapis, N., Artzner, F., Bejjani, R. A., Thillaye-Goldenberg, B., … Behar-Cohen, F. (2006). Oligonucleotide-polyethylenimine complexes targeting retinal cells: Structural analysis and application to anti-TGFβ-2 therapy. Pharmaceutical Research, 23(4), 770–781. https://doi.org/10.1007/s11095-006-9748-0
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