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Corneal chemical burn treatment through a delivery system consisting of TGF-β1 siRNA: in vitro and in vivo

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Abstract

Chemical burns are major causes of corneal blindness. Transforming growth factor beta-1 (TGFβ1) plays an important role in induction of corneal inflammation-related-fibrosis leading to the blindness. Here, a topical delivery system consisting anti-fibrotic TGF-β1 siRNA, an inflammatory suppressing gene, was designed for treatment of corneal injuries. TGF-β1 siRNA loaded in nanoparticles (NPs) made up of polyethyleneimine polymer demonstrated high fibroblast transfection efficiency. Moreover, TGF-β1 and PDGF genes and ECM deposition were suppressed in isolated human corneal fibroblasts. NPs inhibited proliferation and transformation of fibroblasts to myofibroblasts by S-phase arrest and α-SMA suppression in vitro, respectively. The mentioned finding was also confirmed in vivo, addressing high wound-healing potential of prepared gene delivery system which was superior to conventional betamethasone treatment. Besides, CD4+ and α-SMA antibody staining showed inhibited angiogenesis and myofibroblast accumulation in treated corneas. This study opens a new way for treating corneal fibrosis through topical siRNA delivery.

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Authors and Affiliations

  1. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, 14174, Iran

    Forouhe Zahir-Jouzdani, Fatemeh Mottaghitalab, Faezeh Vakhshite, Rasoul Dinarvand & Fatemeh Atyabi

  2. Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Forouhe Zahir-Jouzdani, Fatemeh Mottaghitalab, Faezeh Vakhshite, Rasoul Dinarvand & Fatemeh Atyabi

  3. Bonyakhteh Stem Cell Research Center, Tehran, Iran

    Masoud Soleimani

  4. Noor Ophthalmology Research Center, Noor Eye Hospital, Tehran, Iran

    Mirgholamreza Mahbod & Saeed Shahhoseini

  5. Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran

    Ehsan Arefian

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  1. Forouhe Zahir-Jouzdani
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Zahir-Jouzdani, F., Soleimani, M., Mahbod, M. et al. Corneal chemical burn treatment through a delivery system consisting of TGF-β1 siRNA: in vitro and in vivo. Drug Deliv. and Transl. Res. 8, 1127–1138 (2018). https://doi.org/10.1007/s13346-018-0546-0

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