Norepinephrine as an Enhancer Promoting Corneal Penetration of Riboflavin for Transepithelial Corneal Crosslinking.
Norepinephrine as an Enhancer Promoting Corneal Penetration of Riboflavin for Transepithelial Corneal Crosslinking.
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DOI：
10.1167/tvst.12.2.21
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发表时间：
2023-02-01
影响因子：
3
通讯作者：
Du, Xianli
中科院分区：
文献类型：
--
作者：
Liu, Guoying;Li, Tan;Qi, Benxiang;Gong, Ganyu;Guo, Tengyou;Zhou, Qingjun;Jhanji, Vishal;Zhang, Bi Ning;Du, Xianli
我们以前发现去甲肾上腺素（NE）会影响角膜上皮的完整性，在此我们研究了NE作为化学促进剂在经上皮角膜交联（CXL）过程中促进核黄素角膜渗透的可行性和安全性。确定了在C57 BL/6小鼠中可以促进核黄素扩散通过健康上皮屏障而不诱导上皮损伤的NE的剂量。NE治疗的安全性通过整个角膜的形态学和组织学检查来证实。用裂隙灯、扫描电镜及角膜生物力学测试等方法验证NE促进核黄素穿透的作用。为了更好地适应临床情况，进一步评估了增加NE剂量和缩短核黄素渗透时间。促进核黄素经上皮渗透的NE（1 mg/mL）的最低剂量为2 µL。NE治疗后未观察到可见的角膜结构改变。扫描电镜显示角膜上皮细胞间连接分离。观察到核黄素在整个角膜基质中均匀分布。NE治疗的角膜在CXL后达到了与用市售的经上皮药物Peschke TE治疗的角膜相当的生物力学特性，包括应力松弛曲线和弹性模量。为了更好地适应临床情况，将NE增加至5.5 μL有助于核黄素在30分钟内渗透角膜基质。在使用9 mW/cm 2紫外线-A（UVA）的CXL 2.5分钟后，角膜显示出显著增强的角膜生物力学特性，角膜内皮未受干扰。NE是一种有效的核黄素扩散促进剂，对角膜上皮损伤小，具有很大的临床应用潜力。NE作为核黄素渗透和临床经上皮CXL的有效增强剂。
Previously, we found norepinephrine (NE) could affect the corneal epithelial integrity, herein we investigated the feasibility and safety of NE serving as a chemical enhancer to promote corneal penetration of riboflavin during transepithelial corneal crosslinking (CXL). The dosage of NE that could promote riboflavin diffusion through the healthy epithelial barrier without inducing epithelial damage in C57BL/6 mice was determined. The safety of NE treatment was confirmed by morphological and histological examinations of the whole cornea. The efficacy of NE in promoting riboflavin penetration was verified by slit lamp and scanning electron microscope (SEM), and corneal biomechanical measurement after CXL. To better fit the clinical scenario, increased NE dosage and shortened riboflavin infiltration time were further evaluated. The lowest dosage of NE (1 mg/mL) that facilitated transepithelial riboflavin permeation was 2 µL. No visible corneal structure alteration was observed after NE treatment. SEM indicated dissociation of intercellular junctions among corneal epithelial cells. Homogenous distribution of riboflavin throughout corneal stroma was observed. NE-treated corneas reached comparable biomechanical properties after CXL, including stress-relaxation curve and elastic modulus, with corneas treated with the commercially available transepithelial drug Peschke TE. To better fit the clinical scenario, increasing NE up to 5.5 µL helped riboflavin infiltrate the corneal stroma within 30 minutes. After CXL with 9 mW/cm2 ultraviolet-A (UVA) for 2.5 minutes, the cornea showed significantly enhanced corneal biomechanical properties with undisturbed corneal endothelium. NE serves as an effective enhancer in increasing riboflavin diffusion with limited impairment on corneal epithelium and has great potential for clinical application. NE serves as an effective enhancer for riboflavin penetration and clinical transepithelial CXL.