| Literature DB >> 29869292 |
Forouhe Zahir-Jouzdani1,2, Masoud Soleimani3, Mirgholamreza Mahbod4, Fatemeh Mottaghitalab1,2, Faezeh Vakhshite1,2, Ehsan Arefian5, Saeed Shahhoseini4, Rasoul Dinarvand1,2, Fatemeh Atyabi6,7.
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.Entities:
Keywords: Angiogenesis; Corneal haze; Myofibroblasts; Polyethyleneimine; TGF-β1 siRNA
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Year: 2018 PMID： 29869292 DOI： 10.1007/s13346-018-0546-0
Source DB: PubMed Journal: Drug Deliv Transl Res ISSN： 2190-393X Impact factor: 4.617