Department of Ophthalmology, Eye Repair Lab, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Department of Cell Biology-Inspired Tissue Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, The Netherlands.
Transl Vis Sci Technol. 2024 Feb 1;13(2):9. doi: 10.1167/tvst.13.2.9.
This study aims to assess the efficacy of two aprepitant formulations (X1 and X2), in a preclinical model of dry eye disease (DED) induced by benzalkonium chloride (BAK).
Two aprepitant formulations were tested on 7 to 8-week-old male mice for their efficacy. In vivo corneal fluorescein staining assessed epithelial damage as the primary end point on days 0, 3, 5, 7, 9, 12, and 14 using slit-lamp microscopy. The DED model was induced with 0.2% BAK twice daily for the first week and once daily for the next week. Mice were randomly assigned to 5 treatment groups: Aprepitant X1 (n = 10) and X2 (n = 10) formulation, 2 mg/mL dexamethasone (n = 10), control vehicle X (n = 10), 0.2% hyaluronic acid (n = 10), or no treatment (n = 10). Eye wiping, phenol red, and Cochet Bonnet tests assessed ocular pain, tear fluid secretion, and nerve function. After 7 days, the mice were euthanized to quantify leukocyte infiltration and corneal nerve density.
Topical aprepitant X1 reduced BAK-induced corneal damage and pain compared to gel vehicle X (P = 0.007) and dexamethasone (P = 0.021). Aprepitant X1 and X2 improved corneal sensitivity versus gel vehicle X and dexamethasone (P < 0.001). Aprepitant X1 reduced leukocyte infiltration (P < 0.05) and enhanced corneal nerve density (P < 0.001). Tear fluid secretion remained statistically unchanged in both the X1 and X2 groups.
Aprepitant formulation X1 reduced pain, improved corneal sensitivity and nerve density, ameliorated epitheliopathy, and reduced leukocyte infiltration in male mouse corneas.
Aprepitant emerges as a safe, promising therapeutic prospect for the amelioration of DED's associated symptoms.
本研究旨在评估两种阿瑞匹坦制剂（X1 和 X2）在苯扎氯铵（BAK）诱导的干眼症（DED）的临床前模型中的疗效。
对 7 至 8 周龄雄性小鼠进行两种阿瑞匹坦制剂的功效测试。使用裂隙灯显微镜，在第 0、3、5、7、9、12 和 14 天，通过角膜荧光素染色评估上皮损伤，作为主要终点。DED 模型通过每天两次给予 0.2% BAK 诱导第一周，然后每周一次诱导下一周。将小鼠随机分为 5 个治疗组：阿瑞匹坦 X1（n=10）和 X2（n=10）制剂、2mg/mL 地塞米松（n=10）、对照载体 X（n=10）、0.2%透明质酸（n=10）或不治疗（n=10）。眼擦拭、酚红和 Cochet Bonnet 试验评估眼痛、泪液分泌和神经功能。7 天后，处死小鼠以量化白细胞浸润和角膜神经密度。
与凝胶载体 X（P=0.007）和地塞米松（P=0.021）相比，局部阿瑞匹坦 X1 减少了 BAK 诱导的角膜损伤和疼痛。阿瑞匹坦 X1 和 X2 改善了角膜敏感性，优于凝胶载体 X 和地塞米松（P<0.001）。阿瑞匹坦 X1 减少了白细胞浸润（P<0.05）并增强了角膜神经密度（P<0.001）。X1 和 X2 组的泪液分泌均无统计学差异。
阿瑞匹坦制剂 X1 减少了疼痛，改善了角膜敏感性和神经密度，改善了上皮病变，并减少了雄性小鼠角膜中的白细胞浸润。
本研究旨在评估两种阿瑞匹坦制剂（X1 和 X2）在苯扎氯铵（BAK）诱导的干眼症（DED）的临床前模型中的疗效。
对 7 至 8 周龄雄性小鼠进行两种阿瑞匹坦制剂的功效测试。使用裂隙灯显微镜，在第 0、3、5、7、9、12 和 14 天，通过角膜荧光素染色评估上皮损伤，作为主要终点。DED 模型通过每天两次给予 0.2% BAK 诱导第一周，然后每周一次诱导下一周。将小鼠随机分为 5 个治疗组：阿瑞匹坦 X1（n=10）和 X2（n=10）制剂、2mg/mL 地塞米松（n=10）、对照载体 X（n=10）、0.2%透明质酸（n=10）或不治疗（n=10）。眼擦拭、酚红和 Cochet Bonnet 试验评估眼痛、泪液分泌和神经功能。7 天后，处死小鼠以量化白细胞浸润和角膜神经密度。
与凝胶载体 X（P=0.007）和地塞米松（P=0.021）相比，局部阿瑞匹坦 X1 减少了 BAK 诱导的角膜损伤和疼痛。阿瑞匹坦 X1 和 X2 改善了角膜敏感性，优于凝胶载体 X 和地塞米松（P<0.001）。阿瑞匹坦 X1 减少了白细胞浸润（P<0.05）并增强了角膜神经密度（P<0.001）。X1 和 X2 组的泪液分泌均无统计学差异。
阿瑞匹坦制剂 X1 减少了疼痛，改善了角膜敏感性和神经密度，改善了上皮病变，并减少了雄性小鼠角膜中的白细胞浸润。
