BACKGROUND The cornea is innervated with a rich supply of sensory nerves that play important roles in ocular surface health. Any injury or pathology of the corneal nerves increases the risk of dry eye disease and infection. This study aims to evaluate the therapeutic potential of topical decorin to improve corneal nerve regeneration in a mouse model of sterile epithelial abrasion injury. METHODS Bilateral central corneal epithelial abrasions (2-mm, Alger Brush) were performed on young C57BL/6 J mice to remove the corneal sensory nerves. Decorin, or vehicle, was applied topically, three times per day for 1 week or every 2 h for 6 h. Spectral-domain optical coherence tomography was performed to measure the abrasion area and corneal thickness. Wholemount immunofluorescence staining was used to assess sensory nerve regeneration (β-tubulin III) and immune cell density (CD45, Iba1, CD11c). To investigate the specific role of dendritic cells (DCs), Cx3cr1gfp/gfp mice, which spontaneously lack resident corneal epithelial DCs, were also investigated. The effect of prophylactic topical administration of recombinant human decorin (applied prior to the abrasion) was also investigated. Nerve tracing (NeuronJ software) was performed to compare recovery of basal nerve axons and superficial nerve terminals in the central and peripheral cornea. RESULTS At 6 h after injury, topical decorin application was associated with greater intraepithelial DC recruitment but no change in re-epithelialisation or corneal thickness, compared to the vehicle control. One week after injury, sub-basal nerve plexus and superficial nerve terminal density were significantly higher in the central cornea in the decorin-treated eyes. The density of corneal stromal macrophages in the decorin-treated eyes and their contralateral eyes was significantly lower compared to saline-treated corneas. No significant improvement in corneal nerve regeneration was observed in Cx3cr1gfp/gfp mice treated with decorin. CONCLUSIONS Decorin promotes corneal epithelial nerve regeneration after injury. The neuroregenerative effect of topical decorin was associated with a higher corneal DC density during the acute phase, and fewer macrophages at the study endpoint. The corneal neuroregenerative effects of decorin were absent in mice lacking intraepithelial DCs. Together, these findings support a role for decorin in DC-mediated neuroregeneration following corneal abrasion injury.

中文翻译：

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局部核心蛋白聚糖对受伤小鼠角膜的神经再生作用。

背景角膜受丰富的感觉神经支配，这些感觉神经在眼表健康中起重要作用。角膜神经的任何损伤或病理都会增加干眼病和感染的风险。本研究旨在评估局部核心蛋白聚糖在无菌上皮磨损损伤小鼠模型中改善角膜神经再生的治疗潜力。方法对年轻的 C57BL/6 J 小鼠进行双侧中央角膜上皮擦伤（2 毫米，Alger Brush）以去除角膜感觉神经。核心蛋白聚糖或赋形剂局部应用，每天 3 次，持续 1 周，或每 2 小时使用一次，持续 6 小时。进行光谱域光学相干断层扫描以测量磨损面积和角膜厚度。Wholemount 免疫荧光染色用于评估感觉神经再生（β-微管蛋白 III）和免疫细胞密度（CD45、Iba1、CD11c）。为了研究树突状细胞 (DC) 的具体作用，还研究了自发缺乏常驻角膜上皮 DC 的 Cx3cr1gfp/gfp 小鼠。还研究了预防性局部施用重组人核心蛋白聚糖（在磨损前应用）的效果。进行神经追踪（NeuronJ 软件）以比较中央和周围角膜中基底神经轴突和浅表神经末梢的恢复情况。结果在受伤后 6 小时，与载体对照相比，局部使用核心蛋白聚糖与更多的上皮内 DC 募集相关，但上皮再形成或角膜厚度没有变化。受伤一周后，在核心蛋白聚糖治疗的眼睛中，中央角膜的基底下神经丛和浅表神经末梢密度显着更高。与盐水处理的角膜相比，核心蛋白聚糖处理的眼睛及其对侧眼中角膜基质巨噬细胞的密度显着降低。在用核心蛋白聚糖处理的 Cx3cr1gfp/gfp 小鼠中没有观察到角膜神经再生的显着改善。结论 核心蛋白聚糖促进损伤后角膜上皮神经再生。局部核心蛋白聚糖的神经再生作用与急性期较高的角膜 DC 密度和研究终点的巨噬细胞较少有关。缺乏上皮内 DCs 的小鼠不存在核心蛋白聚糖的角膜神经再生作用。一起，