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Background <p>Animal models that simultaneously reproduce neurotrophic keratopathy (NK) and limbal stem cell deficiency (LSCD) are scarce, despite the frequent clinical coexistence of these two conditions. We aimed to establish a reproducible rat model showing a combined NK/LSCD phenotype by selectively injuring the ophthalmic branch of the trigeminal nerve (V1) within the orbit.</p> Methods <p>Adult male Sprague–Dawley rats underwent intraorbital V1 transection or V1 exposure without transection. Corneal sensitivity was evaluated qualitatively using a cotton-swab touch response and quantitatively using a Cochet–Bonnet esthesiometer before surgery and on postoperative days 7, 14, and 21. Tear secretion, fluorescein staining, ocular surface abnormalities, and corneal neovascularization were assessed longitudinally. Corneal and limbal tissues were examined histologically and by PAS staining, CD31, K12, K14, and P63 immunostaining, and TUNEL analysis.</p> Results <p>Cochet–Bonnet esthesiometry confirmed profound corneal hypoesthesia after V1 injury. Corneal sensitivity remained at 60&#xa0;mm before surgery and in sham eyes at all postoperative time points, whereas the mean thresholds in the V1-injury group were 3.5&#xa0;mm, 4.0&#xa0;mm, and 5.5&#xa0;mm on postoperative days 7, 14, and 21, respectively. V1 injury was also associated with reduced tear secretion, persistent epithelial compromise, progressive corneal neovascularization, stromal fibrosis, PAS-positive goblet-cell invasion, reduced limbal P63 and K14 expression, peripheral loss of K12 expression, and increased corneal apoptosis.</p> Conclusions <p>Intraorbital V1 injury induces a denervation-associated ocular surface disease phenotype with overlapping features of neurotrophic keratopathy and secondary limbal epithelial failure in rats. Within the 21-day observation period, this model provides a practical platform for investigating early-to-intermediate interactions between corneal sensory denervation, epithelial dysfunction, and limbal niche disturbance. Its long-term stability and the course of corneal reinnervation remain to be determined.</p>

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A novel rat model of neurotrophic keratopathy complicated with limbal stem cell deficiency induced by trigeminal ophthalmic branch injury

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月11日

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  • Xiaorong Sun,
  • Yue Chen,
  • Dan Su,
  • Feng Luo,
  • Min Zhang,
  • Yuwei Xu,
  • Jinliang Yang

摘要

Background

Animal models that simultaneously reproduce neurotrophic keratopathy (NK) and limbal stem cell deficiency (LSCD) are scarce, despite the frequent clinical coexistence of these two conditions. We aimed to establish a reproducible rat model showing a combined NK/LSCD phenotype by selectively injuring the ophthalmic branch of the trigeminal nerve (V1) within the orbit.

Methods

Adult male Sprague–Dawley rats underwent intraorbital V1 transection or V1 exposure without transection. Corneal sensitivity was evaluated qualitatively using a cotton-swab touch response and quantitatively using a Cochet–Bonnet esthesiometer before surgery and on postoperative days 7, 14, and 21. Tear secretion, fluorescein staining, ocular surface abnormalities, and corneal neovascularization were assessed longitudinally. Corneal and limbal tissues were examined histologically and by PAS staining, CD31, K12, K14, and P63 immunostaining, and TUNEL analysis.

Results

Cochet–Bonnet esthesiometry confirmed profound corneal hypoesthesia after V1 injury. Corneal sensitivity remained at 60 mm before surgery and in sham eyes at all postoperative time points, whereas the mean thresholds in the V1-injury group were 3.5 mm, 4.0 mm, and 5.5 mm on postoperative days 7, 14, and 21, respectively. V1 injury was also associated with reduced tear secretion, persistent epithelial compromise, progressive corneal neovascularization, stromal fibrosis, PAS-positive goblet-cell invasion, reduced limbal P63 and K14 expression, peripheral loss of K12 expression, and increased corneal apoptosis.

Conclusions

Intraorbital V1 injury induces a denervation-associated ocular surface disease phenotype with overlapping features of neurotrophic keratopathy and secondary limbal epithelial failure in rats. Within the 21-day observation period, this model provides a practical platform for investigating early-to-intermediate interactions between corneal sensory denervation, epithelial dysfunction, and limbal niche disturbance. Its long-term stability and the course of corneal reinnervation remain to be determined.