{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:17:54Z","timestamp":1787764674591,"version":"build-2784847793"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>JOURNAL\/nrgr\/04.03\/01300535-202403000-00045\/inline-graphic1\/v\/2023-09-27T141015Z\/r\/image-tiff<\/jats:p>\n                  <jats:p>\n                    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\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . 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\u2019s 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 &lt; 5. Moreover, best corrected visual acuity, intraocular pressure, Schirmer\u2019s test and Cochet-Bonnet corneal perception test results showed no significant improvement. An increase in corneal nerve density was observed by\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    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 in all eyes with neurotrophic keratopathy suggests CTH-mNGF has promising application prospects in the treatment of neurotrophic keratopathy, being convenient and cost effective.\n                  <\/jats:p>","DOI":"10.4103\/1673-5374.380908","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T13:07:46Z","timestamp":1691759266000},"page":"680-686","source":"Crossref","is-referenced-by-count":10,"title":["Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy"],"prefix":"10.4103","volume":"19","author":[{"given":"Jie","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, the Third Medical Center, Chinese PLA General Hospital, Beijing, China"},{"name":"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"},{"name":"Department of Ophthalmology, Hainan Hospital of Chinese PLA General Hospital, Sanya, Hainan Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulei","family":"Huang","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanrui","family":"Yu","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaixiu","family":"Li","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Medical School of Chinese PLA, Beijing, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwok-Fai","family":"So","sequence":"additional","affiliation":[{"name":"Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou, Guangdong Province, China"},{"name":"Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, Guangdong Province, China"},{"name":"Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong Special Administrative Region, China"},{"name":"Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong-Macao Greater Bay Area, Guangzhou, Guangdong Province, China"},{"name":"Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8313-6998","authenticated-orcid":false,"given":"Zhaoyang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-3676","authenticated-orcid":false,"given":"Xiaoguang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China"},{"name":"School of Engineering Medicine, Beijing Key Laboratory for Biomaterials and Neural Regeneration, Beihang University, Beijing, China"},{"name":"Beijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang 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