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

作者: Parimala Nacharaju , Adam Kramer , Abhinav Dey , David Sharp , Lisa Baker

DOI: 10.1101/2020.06.18.159533

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摘要: PurposeTo determine the efficacy of nanoparticle-encapsulated FL2 siRNA (FL2-NPsi), a novel therapeutic agent targeting Fidgetin-like 2 (FL2) gene, for treatment corneal alkaline chemical injury. MethodsEighty 12-week-old, male Sprague-Dawley rats were divided evenly into 8 groups: prednisolone, empty nanoparticles, control-NPsi (1 M, 10 20 M) and FL2-NPsi M). An burn was induced onto cornea each rat, which then treated 14 days according to group assignment. Clinical (N=10 per group), histopathologic (N=6 immunohistochemical (N=4 group) analyses conducted assess wound healing. FL2-NPsi-mediated knockdown confirmed by in vitro qPCR. Toxicity assays performed apoptosis (TUNEL assay, N=3 nerve damage (whole mount immunochemical staining, N=2 group). Statistical using students t-test ANOVA. ResultsCompared controls, FL2-NPsi-treated groups demonstrated enhanced healing, with M demonstrating maximum rates re-epithelialization (p=0.0003 at Day 4 p<0.0001 8) as assessed ImageJ software, transparency, improved stromal organization on histology. Immunohistochemical analysis vascular endothelial cells, macrophages, neutrophils did not show significant differences between groups. found be toxic nerves or induce (p=0.917). ConclusionDose-response studies both efficacious this rat model. may offer injuries.

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