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干眼患者与正常受试者角膜瞬时受体电位香草酸亚型8(TRPM8)受体对薄荷醇滴入的动态敏感性

Dynamic Sensitivity of Corneal TRPM8 Receptors to Menthol Instillation in Dry Eye Versus Normal Subjects.

作者信息

Corcoran Peter, Hollander David A, Ousler George W, Angjeli Endri, Rimmer David, Lane Keith, Abelson Mark B

机构信息

1 Ora, Inc. , Andover, Massachusetts.

2 Jules Stein Eye Institute, University of Southern California , Los Angeles, California.

出版信息

J Ocul Pharmacol Ther. 2017 Nov;33(9):686-692. doi: 10.1089/jop.2017.0050. Epub 2017 Sep 21.

Abstract

PURPOSE

To assess the sensitivity of corneal cold receptors to a known transient receptor potential melastatin 8 (TRPM8) agonist, menthol, in dry eye and normals, and to determine whether factors such as disease duration or age affect responses.

METHODS

Dry eye disease (DED) (N = 33) and normal (N = 15) subjects were randomly assigned to receive Rohto Hydra (0.01% menthol) or Systane Ultra treatments (OU) in a prospective, double-blind, crossover study. DED subjects had documented disease and symptom response scores >2 on a 0- to 5-point scale. Normals had no history of DED and scores <2 on the same scale. Endpoints included mean cooling score (0 = not cool and 10 = very cool) evaluated at 0, 0.5, 1, 2, 3, and 4 min post-instillation, sum cooling scores (5 time points, range 0-60), and ocular signs and symptoms.

RESULTS

Mean (±SD) ages were similar, 62.2 ± 8.6-year (DED) versus 53.5 ± 7.6-year (normal). Corneal sensitivity scores were not different between groups. Mean cooling scores at 0.5-4 min post-menthol instillation were significantly higher in DED subjects (P ≤ 0.03). Sum cooling scores were significantly higher (P = 0.04) in DED subjects with a disease duration <10 years (N = 18, 28.3 ± 2.58) versus ≥10 years (N = 15, 20.2 ± 2.76). Age did not affect cooling response in either group.

CONCLUSION

DED subjects had greater sensitivity to cold than normal subjects. DED duration, and not age, was critical to cooling sensitivity. The finding that cooling scores were higher in subjects with DED for less than 10 years compared to more than 10 years suggests that corneal cold receptor sensitivity decreases as the duration of DED increases.

摘要

目的

评估干眼患者和正常人角膜冷感受器对已知的瞬时受体电位香草酸亚型8(TRPM8)激动剂薄荷醇的敏感性,并确定疾病持续时间或年龄等因素是否会影响反应。

方法

在一项前瞻性、双盲、交叉研究中,将干眼疾病(DED)患者(N = 33)和正常人(N = 15)随机分配接受乐敦莹(0.01%薄荷醇)或思然眼药水(OU)治疗。DED患者有记录在案的疾病,症状反应评分在0至5分制中>2分。正常人无DED病史,在同一评分制中评分<2分。观察指标包括滴入后0、0.5、1、2、3和4分钟时评估的平均冷却评分(0 = 不凉,10 = 非常凉)、总冷却评分(5个时间点,范围0 - 60)以及眼部体征和症状。

结果

平均(±标准差)年龄相似,干眼组为62.2 ± 8.6岁,正常组为53.5 ± 7.6岁。两组间角膜敏感性评分无差异。薄荷醇滴入后0.5 - 4分钟时,DED患者的平均冷却评分显著更高(P≤0.03)。疾病持续时间<10年的DED患者(N = 18,28.3 ± 2.58)的总冷却评分显著高于疾病持续时间≥10年的患者(N = 15,20.2 ± 2.76)(P = 0.04)。年龄对两组的冷却反应均无影响。

结论

DED患者对冷的敏感性高于正常人。DED的持续时间而非年龄对冷却敏感性至关重要。与病程超过10年的患者相比,病程小于10年的DED患者冷却评分更高,这一发现表明随着DED持续时间的增加,角膜冷感受器敏感性降低。

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