Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy  

作　　者：Jie Wu Yulei Huang Hanrui Yu Kaixiu Li Shifeng Zhang Guoqing Qiao Xiao Liu Hongmei Duan Yifei Huang Kwok-Fai So Zhaoyang Yang Xiaoguang Li Liqiang Wang 

机构地区：[1]Department of Ophthalmology,the Third Medical Center,Chinese PLA General Hospital,Beijing,China [2]The PLA Medical College,Department of Nephrology,Chinese PLA Institute of Nephrology,State Key Laboratory of Kidney Diseases,National Clinical Research Center for Kidney Diseases,Beijing,China [3]Department of Ophthalmology,Hainan Hospital of Chinese PLA General Hospital,Sanya,Hainan Province,China [4]Medical School of Chinese PLA,Beijing,China [5]Department of Neurobiology,School of Basic Medical Sciences,Capital Medical University,Beijing,China [6]Guangdong-Hongkong-Macao Institute of CNS Regeneration,Ministry of Education CNS Regeneration Collaborative Joint Laboratory,Jinan University,Guangzhou,Guangdong Province,China [7]Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory),Guangzhou,Guangdong Province,China [8]Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences,The University of Hong Kong,Hong Kong Special Administrative Region,China [9]Center for Brain Science and Brain-Inspired Intelligence,Guangdong-Hong Kong-Macao Greater Bay Area,Guangzhou,Guangdong Province,China [10]Co-innovation Center of Neuroregeneration,Nantong University,Nantong,Jiangsu Province,China [11]School of Engineering Medicine,Beijing Key Laboratory for Biomaterials and Neural Regeneration,Beihang University,Beijing,China [12]Beijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration,Beijing Advanced Innovation Center for Big Data-Based Precision Medicine,Beihang University,Beijing,China

出　　处：《Neural Regeneration Research》2024年第3期680-686,共7页中国神经再生研究（英文版）

基　　金：supported by PLA General Hospital Program,No.LB20201A010024(to LW).

摘　　要：Neurotrophic keratopathy is a persistent defect of the corneal epithelium,with or without stromal ulceration,due to corneal nerve deficiency caused by a variety of etiologies.The treatment options for neurotrophic keratopathy are limited.In this study,an ophthalmic solution was constructed from a chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor(CTH-mNGF).Its effectiveness was evaluated in corneal denervation(CD)mice and patients with neurotrophic keratopathy.In the preclinical setting,CTH-mNGF was assessed in a murine corneal denervation model.CTH-mNGF was transparent,thermosensitive,and ensured sustained release of mNGF for over 20 hours on the ocular surface,maintaining the local mNGF concentration around 1300 pg/mL in vivo.Corneal denervation mice treated with CTH-mNGF for 10 days showed a significant increase in corneal nerve area and total corneal nerve length compared with non-treated and CTH treated mice.A subsequent clinical trial of CTH-mNGF was conducted in patients with stage 2 or 3 neurotrophic keratopathy.Patients received topical CTH-mNGF twice daily for 8 weeks.Fluorescein sodium images,Schirmer’s test,intraocular pressure,Cochet-Bonnet corneal perception test,and best corrected visual acuity were evaluated.In total,six patients(total of seven eyes)diagnosed with neurotrophic keratopathy were enrolled.After 8 weeks of CTH-mNGF treatment,all participants showed a decreased area of corneal epithelial defect,as stained by fluorescence.Overall,six out of seven eyes had fluorescence staining scores<5.Moreover,best corrected visual acuity,intraocular pressure,Schirmer’s test and Cochet-Bonnet corneal perception test results showed no significant improvement.An increase in corneal nerve density was observed by in vivo confocal microscopy after 8 weeks of CTH-mNGF treatment in three out of seven eyes.This study demonstrates that CTH-mNGF is transparent,thermosensitive,and has sustained-release properties.Its effectiveness in healing corneal epithelial defects

关 键 词：chitosan corneal reinnervation murine nerve growth factor neurotrophic keratopathy thermosensitive hydrogel 

分 类 号：R772.2[医药卫生—眼科]