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

Chi Hsien Peng, Jong Yuh Cherng, Guang-Yuh Chiou, Yu Chih Chen, Chen Hsiu Chien, Chung Lan Kao, Yuh Lih Chang, Yueh Chien, Liang Kung Chen, Jorn hon Liu, Shih Jen Chen, Shih Hwa Chiou*

*Corresponding author for this work

Research output: Contribution to journalArticle

34 Scopus citations

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.

Original languageEnglish
Pages (from-to)9077-9088
Number of pages12
JournalBiomaterials
Volume32
Issue number34
DOIs
StatePublished - 1 Dec 2011

Keywords

  • Age-related macular degeneration
  • Oct4
  • Polyurethane-short branch polyethylenimine
  • Reprogramming
  • Retinal pigment epithelium cells
  • SirT1

Fingerprint Dive into the research topics of 'Delivery of Oct4 and SirT1 with cationic polyurethanes-short branch PEI to aged retinal pigment epithelium'. Together they form a unique fingerprint.

  • Cite this

    Peng, C. H., Cherng, J. Y., Chiou, G-Y., Chen, Y. C., Chien, C. H., Kao, C. L., Chang, Y. L., Chien, Y., Chen, L. K., Liu, J. H., Chen, S. J., & Chiou, S. H. (2011). Delivery of Oct4 and SirT1 with cationic polyurethanes-short branch PEI to aged retinal pigment epithelium. Biomaterials, 32(34), 9077-9088. https://doi.org/10.1016/j.biomaterials.2011.08.008