“A novel therapeutic approach to corneal alkaline burn model by targeting Fidgetin-like 2, a microtubule regulator”

作者: Jessie Wang , Abhinav Dey , Adam Kramer , Yuan Miao , Juan Liu

DOI: 10.1101/2020.06.18.159533

关键词:

摘要: Purpose The purpose of this study was to determine the efficacy nanoparticle-encapsulated Fidgetin-like 2 (FL2) siRNA (FL2-NPsi), a novel therapeutic agent targeting FL2 gene, for treatment corneal alkaline chemical injury. Methods Eighty 12-week-old, male Sprague-Dawley rats were divided evenly into 8 groups: prednisolone, empty nanoparticles, control-NPsi (1 µM, 10 and 20 µM) FL2-NPsi µM). An burn induced onto cornea each rat, which then treated 14 days according group assignment. Clinical, histopathologic, immunohistochemical analyses conducted assess wound healing. FL2-NPsi-mediated knockdown confirmed by in vitro quantitative polymerase chain reaction (qPCR). Toxicity assays performed apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling [TUNEL] assay) nerve damage (whole mount immunochemical staining). Statistical using Student's t-test ANOVA. Results Compared with controls, FL2-NPsi-treated groups demonstrated enhanced healing, µM demonstrating maximum rates re-epithelialization 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). Conclusions Dose-response studies both efficacious rat model. may offer injuries. Translational relevance Basic cell biology findings about microtubule cytoskeleton used design enhance migration, highlighting promise microtubules regulate

参考文章(37)
Parul Singh, Manoj Tyagi, Yogesh Kumar, KK Gupta, PD Sharma, None, Ocular chemical injuries and their management Oman Journal of Ophthalmology. ,vol. 6, pp. 83- 86 ,(2013) , 10.4103/0974-620X.116624
K. Phillips, R. Arffa, C. Cintron, J. Rose, D. Miller, C. L. Kublin, K. R. Kenyon, Effects of Prednisolone and Medroxyprogesterone on Corneal Wound Healing, Ulceration, and Neovascularization Archives of Ophthalmology. ,vol. 101, pp. 640- 643 ,(1983) , 10.1001/ARCHOPHT.1983.01040010640024
Michael D. Wagoner, Chemical injuries of the eye: current concepts in pathophysiology and therapy. Survey of Ophthalmology. ,vol. 41, pp. 275- 313 ,(1997) , 10.1016/S0039-6257(96)00007-0
C. HANNA, D. S. BICKNELL, J. E. O'BRIEN, Cell turnover in the adult human eye. Archives of Ophthalmology. ,vol. 65, pp. 695- 698 ,(1961) , 10.1001/ARCHOPHT.1961.01840020697016
Chastain Anderson, Qinbo Zhou, Shusheng Wang, An alkali-burn injury model of corneal neovascularization in the mouse. Journal of Visualized Experiments. pp. 51159- ,(2014) , 10.3791/51159
Ou Xiao, Zhao-lian Xie, Bin-wu Lin, Xiao-fang Yin, Rong-biao Pi, Shi-you Zhou, Minocycline Inhibits Alkali Burn-Induced Corneal Neovascularization in Mice PLoS ONE. ,vol. 7, pp. e41858- ,(2012) , 10.1371/JOURNAL.PONE.0041858
Christopher T. Turner, Morteza Hasanzadeh Kafshgari, Elizabeth Melville, Bahman Delalat, Francis Harding, Ermei Mäkilä, Jarno J. Salonen, Allison J. Cowin, Nicolas H. Voelcker, Delivery of Flightless I siRNA from Porous Silicon Nanoparticles Improves Wound Healing in Mice. ACS Biomaterials Science & Engineering. ,vol. 2, pp. 2339- 2346 ,(2016) , 10.1021/ACSBIOMATERIALS.6B00550
Rabab A. Charafeddine, Joy Makdisi, David Schairer, Brian P. O'Rourke, Juan D. Diaz-Valencia, Jason Chouake, Allison Kutner, Aimee Krausz, Brandon Adler, Parimala Nacharaju, Hongying Liang, Suranjana Mukherjee, Joel M. Friedman, Adam Friedman, Joshua D. Nosanchuk, David J. Sharp, Fidgetin-Like 2: A Microtubule-Based Regulator of Wound Healing Journal of Investigative Dermatology. ,vol. 135, pp. 2309- 2318 ,(2015) , 10.1038/JID.2015.94
Tamara Martínez, Maria Victoria González, Ingo Roehl, Natalia Wright, Covadonga Pañeda, Ana Isabel Jiménez, In Vitro and in Vivo Efficacy of SYL040012, a Novel siRNA Compound for Treatment of Glaucoma Molecular Therapy. ,vol. 22, pp. 81- 91 ,(2014) , 10.1038/MT.2013.216
Mark A. Behlke, Chemical Modification of siRNAs for In Vivo Use Oligonucleotides. ,vol. 18, pp. 305- 320 ,(2008) , 10.1089/OLI.2008.0164