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• W2045803043 abstract "Purpose. Retinal pigment epithelium (RPE) is an interesting target for gene delivery. Transfected RPE cells could serve as a platform for secretion of neurotrophic or angiostatic factors to the neural retina or to retinal and choroideal vessels, respectively. Intravitreal injection of DNA/cationic liposome complexes, so called lipoplexes, would be a clinically feasible and realistic method for gene delivery to the RPE. Previous studies showed that pegylation of lipoplexescan avoid immobilisation in the vitreous. The aim of this study was both to elucidate whether lipoplexes can permeate the neural retina as well as to evaluate strategies to improve the diffusion of these lipoplexes through the neural retina. Methods. A bovine eye model was used to investigate the role of the neural retina as a barrier for RPE gene therapy. The anterior parts and the vitreous of fresh bovine eyes were removed and the neural retina was left intact or peeled away. Subsequently, fluorescent lipoplexes with increasing degree of pegylation, were pipetted on the neural retina or on the RPE. Two hours later the neural retina was removed, if present, and the RPE cells were detached. After removal of contaminants by sucrose centrifugation, the RPE cells were analyzed for lipoplex uptake by flow cytometry. Results. We showed that RPE cells take up non pegylated lipoplexes as well as pegylated lipoplexes. Moreover, increasing the pegylation degree of the lipoplexes did not decrease the cellular internalization by the RPE cells. On the other hand, neural retina severely limits the uptake of lipoplexes by the RPE. Increasing the pegylation degree of the lipoplexes could not overcome the barrier function of the neural retina. Conclusion. The uptake of non pegylated and pegylated lipoplexes by RPE cells is very efficiently. Moreover, inreasing the pegylation degree did not affect the cellular uptake by the RPE cells. Delivery of lipoplexes to the RPE is limited by the neural retina. Although previous studies pointed out that pegylation of lipoplexes can avoid immobilization in the vitreous body, pegylation does not improve the diffusion through the retina significantly. In future, other strategies like, for example ultrasound, can be evaluated to aprove the diffusion through the neural retina." @default.
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• W2045803043 date "2006-01-01" @default.
• W2045803043 modified "2023-10-16" @default.
• W2045803043 title "522. Neural Retina Limits Delivery Non Viral Vectors to Retinal Pigment Epithelium" @default.
• W2045803043 doi "https://doi.org/10.1016/j.ymthe.2006.08.593" @default.
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