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.
authors: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
authors: Chi-Hsien
authors: CH
authors: Peng
authors: Jong-Yuh
authors: JY
authors: Cherng
authors: Guang-Yuh
authors: GY
authors: Chiou
authors: Yu-Chih
authors: YC
authors: Chen
authors: Chen-Hsiu
authors: CH
authors: Chien
authors: Chung-Lan
authors: CL
authors: Kao
authors: Yuh-Lih
authors: YL
authors: Chang
authors: Yueh
authors: Y
authors: Chien
authors: Liang-Kung
authors: LK
authors: Chen
authors: Jorn-hon
authors: JH
authors: Liu
authors: Shih-Jen
authors: SJ
authors: Chen
authors: Shih-Hwa
authors: SH
authors: Chiou
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D050814:Octamer Transcription Factor-3 / Q000008:administration & dosage* / Q000235:genetics*; D011094:Polyethyleneimine / Q000737:chemistry*; D011140:Polyurethanes / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism* / Q000473:pathology; D056564:Sirtuin 1 / Q000008:administration & dosage* / Q000235:genetics*
chemical_list: D050814:Octamer Transcription Factor-3; D011140:Polyurethanes; D011094:Polyethyleneimine; C447939:SIRT1 protein, human; D056564:Sirtuin 1