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Delivery of Oct4 and SirT1 with cationic polyurethanes-short branch PEI to aged retinal pigment epithelium

Paper ID Volume ID Publish Year Pages File Format Full-Text
7129 535 2011 12 PDF Available
Title
Delivery of Oct4 and SirT1 with cationic polyurethanes-short branch PEI to aged retinal pigment epithelium
Abstract

Cationic polyurethane, a biodegradable non-viral vector, protects DNA from nuclease degradation and helps to deliver genes efficiently. Oct4, a POU-domain transcription factor, is highly expressed in maintaining pluripotency and cellular reprogramming process in stem cells. SirT1, a NAD-dependent histone deacetylase, is an essential mediator of cellular longevity. Herein we demonstrated that both Oct4 and SirT1 (Oct4/SirT1) expression was decreased in an age-dependent manner in retina with aged-related macular degeneration and retinal pigment epithelium cells (RPEs). To investigate the possible rescuing role of Oct4/SirT1, polyurethane-short branch polyethylenimine (PU-PEI) was used to deliver Oct4/SirT1 into aged RPEs (aRPEs) or light-injured rat retinas. Oct4/SirT1 overexpression increased the expression of several progenitor-related genes and the self-renewal ability of aRPEs. Moreover, Oct4/SirT1 overexpression resulted in the demethylation of the Oct4 promoter and enhanced the expression of antioxidant enzymes, which was accompanied by a decrease in intracellular ROS production and hydrogen peroxide-induced oxidative stress. Importantly, PU-PEI-mediated Oct4/SirT1 gene transfer rescued retinal cell loss and improved electroretinographic responses in light-injured rat retinas. In summary, these data suggest that PU-PEI-mediated delivery of Oct4/SirT1 reprograms aRPEs into a more primitive state and results in cytoprotection by regulating the antioxidative capabilities of these cells.

Keywords
Polyurethane-short branch polyethylenimine; Oct4; SirT1; Retinal pigment epithelium cells; Age-related macular degeneration; ReprogrammingPolyurethane-short branch polyethylenimine, PU-PEI; Retinal pigment epithelium cells, RPEs; Age-related macular degen
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Delivery of Oct4 and SirT1 with cationic polyurethanes-short branch PEI to aged retinal pigment epithelium
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 34, December 2011, Pages 9077–9088
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us