Corneal Chemical Burn Treatment Through a Delivery System Consisting of Tgf-Β1 Sirna: In Vitro and in Vivo Publisher Pubmed



Zahirjouzdani F^{1, 2} ; Soleimani M³ ; Mahbod M⁴ ; Mottaghitalab F^{1, 2} ; Vakhshite F^{1, 2} ; Arefian E⁵ ; Shahhoseini S⁴ ; Dinarvand R^{1, 2} ; Atyabi F^{1, 2} Show Affiliations
Source: Drug Delivery and Translational Research Published:2018

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. © 2018, Controlled Release Society.