ArticleNeural regeneration research2024
Chitosan-based thermosensitive hydrogel with long-term release of murine nerve growth factor for neurotrophic keratopathy.
Article in Neural regeneration research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed, 6 citations in OpenAlex.
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- Recent Advances in Extended Ocular Drug Delivery for the Ocular Surface.Molecules (Basel, Switzerland) · 2026Review
- Corneal Nerves Promote Alkali Burn Repair by Modulating Macrophages and Neutrophils via Calcitonin Gene-Related Peptide.Investigative ophthalmology & visual science · 2026Article
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 in all eyes with neurotrophic keratopathy suggests CTH-mNGF has promising application prospects in the treatment of neurotrophic keratopathy, being convenient and cost effective.
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