Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, USA.
Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Tianjin, China.
J Ocul Pharmacol Ther. 2024 Sep;40(7):445-451. doi: 10.1089/jop.2024.0003. Epub 2024 Jun 3.
To evaluate the therapeutic efficacy of topical application of a neurokinin-1 receptor (NK1R) antagonist in a rabbit model of nonallergic ocular redness. Nonallergic ocular redness was induced in rabbits by a single, topical application of dapiparzole hydrochloride eye drops (0.5%, 1%, 2%, or 5%). The NK1R antagonist L-703,606 was topically applied to the eye at the same time of induction or 20 min after induction, and phosphate buffered saline (PBS) treatment served as the control. Superior bulbar conjunctival images were taken every 30 s for the first 2 min, followed by every 4 min for 8 min, and then every 10 min until 1 h. The severity of ocular redness was evaluated on the images using ImageJ-based ocular redness index (ORI) calculations. The ORI scores were significantly increased after the application of 0.5%, 1%, 2%, or 5% dapiparzole at each time point evaluated, with the most severe redness induced by the 5% dapiprazole that led to a maximal mean increase in ORI score of 14 at 20 min post-induction and thus used for subsequent evaluation of therapeutic efficacy of NK1R antagonism. Topical L-703,606, when applied at the same time as dapiprazole induction, significantly suppressed the increase of ORI scores at all time points (∼40% decrease). Furthermore, when applied at 20 min after dapiprazole induction, L-703,606 rapidly and effectively suppressed the increase of ORI scores at 30, 40, 50, and 60 min (∼30% decrease). Topical blockade of NK1R effectively prevents and alleviates nonallergic ocular redness in a novel animal model.
评估神经激肽-1 受体 (NK1R) 拮抗剂在兔非变应性眼红模型中的治疗效果。 通过单次局部应用盐酸达匹帕唑滴眼液（0.5%、1%、2%或 5%）在兔子中诱导非变应性眼红。 在诱导的同时或诱导后 20 分钟，将 NK1R 拮抗剂 L-703,606 局部应用于眼部，并用磷酸盐缓冲盐水 (PBS) 处理作为对照。 在最初的 2 分钟内每 30 秒拍摄一次上直肌球结膜图像，然后每 4 分钟拍摄一次 8 分钟，然后每 10 分钟拍摄一次，直到 1 小时。 使用基于 ImageJ 的眼红指数 (ORI) 计算在图像上评估眼红的严重程度。 在评估的每个时间点，应用 0.5%、1%、2%或 5%达匹帕唑后，ORI 评分均显著升高，其中 5%达匹唑诱导的眼红最严重，导致诱导后 20 分钟 ORI 评分最大平均增加 14，因此用于随后评估 NK1R 拮抗作用的治疗效果。 当与达匹帕唑诱导同时应用时，局部 L-703,606 显著抑制 ORI 评分的增加在所有时间点（约 40%减少）。 此外，当在达匹帕唑诱导后 20 分钟应用时，L-703,606 可迅速有效地抑制 30、40、50 和 60 分钟时 ORI 评分的增加（约 30%减少）。 局部阻断 NK1R 可有效预防和缓解新型动物模型中的非变应性眼红。
