A Novel Therapeutic Approach to Corneal Alkaline Burn Model by Targeting Fidgetin-like 2, a Microtubule Regulator

BioRxiv : the Preprint Server for Biology
J. WangDavid Sharp

Abstract

Purpose: To determine the efficacy of nanoparticle-encapsulated FL2 siRNA (FL2-NPsi), a novel therapeutic agent targeting the Fidgetin-like 2 (FL2) gene, for the treatment of corneal alkaline chemical injury. Methods: Eighty 12-week-old, male Sprague-Dawley rats were divided evenly into 8 treatment groups: prednisolone, empty nanoparticles, control-NPsi (1 {micro}M, 10 {micro}M, 20 {micro}M) and FL2-NPsi (1 {micro}M, 10 {micro}M, 20 {micro}M). An alkaline burn was induced onto the cornea of each rat, which was then treated for 14 days according to group assignment. Clinical (N=10 per group), histopathologic (N=6 per group), and immunohistochemical (N=4 per group) analyses were conducted to assess for wound healing. FL2-NPsi-mediated knockdown of FL2 was confirmed by in vitro qPCR. Toxicity assays were performed to assess for apoptosis (TUNEL assay, N=3 per group) and nerve damage (whole mount immunochemical staining, N=2 per group). Statistical analyses were performed using student's t-test and ANOVA. Results: Compared to controls, FL2-NPsi-treated groups demonstrated enhanced corneal wound healing, with the 10 and 20 {micro}M FL2-NPsi-treated groups demonstrating maximum rates of corneal re-epithelialization (p=0.0003 at Day 4...Continue Reading

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