Sebbag Lionel, Allbaugh Rachel A, Weaver Amanda, Seo Yeon-Jung, Mochel Jonathan P
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.
Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.
Front Pharmacol. 2019 Jul 9;10:752. doi: 10.3389/fphar.2019.00752. eCollection 2019.
Conjunctival inflammation disturbs the blood-tear barrier and thus affects the tear film stability and composition. We aimed to develop a non-invasive and reliable method to induce conjunctivitis in dogs, a large animal model for translational work on ocular surface disease in humans. Six beagle dogs underwent a randomized, vehicle-controlled, balanced crossover trial-on six separate days, one eye received topical artificial tears (vehicle), while the other eye received one of six concentrations of histamine solution (0.005-500 mg/ml). At sequential times after eyedrop administration, a conjunctivitis score was given to each eye based on the degree of palpebral and bulbar conjunctival hyperemia and chemosis, ocular pruritus, and discharge. Total protein content (TPC) and serum albumin were quantified in tear fluid at baseline and 20 min. Additionally, 13 dogs presenting for various ophthalmic diseases with associated conjunctivitis were examined. Experimentally induced conjunctivitis developed rapidly (<1 min) following topical histamine administration and lasted for 1-3 h (four lowest doses) to 6-8 h (two highest doses). The severity of conjunctivitis was dose-dependent. Histamine was overall well tolerated, although transient blepharitis, aqueous flare, and ocular hypertension occurred in a few dogs receiving histamine ≥375 mg/ml. TPC and serum albumin levels increased in tears of eyes receiving histamine ≥1.0 mg/ml, being significantly higher than vehicle and baseline in eyes receiving histamine ≥375 mg/ml. Lacrimal albumin levels were also increased in 13 dogs with naturally acquired conjunctivitis, up 2.7-14.9 fold compared to contralateral healthy eyes. Histamine-induced conjunctivitis represents a robust model for translational work on the ocular surface given the low cost, non-invasiveness, self-resolving nature, ability to adjust the duration and severity of the disease, and shared features with naturally occurring ocular diseases. Histamine solutions of 1, 10, and 375 mg/ml induce mild, moderate, and severe conjunctivitis in dogs, respectively. Leakage of serum albumin in tear fluid of eyes with conjunctivitis suggests a breakdown of the blood-tear barrier.
结膜炎症会扰乱血 - 泪屏障，进而影响泪膜稳定性和成分。我们旨在开发一种非侵入性且可靠的方法，在犬类（人类眼表疾病转化研究的大型动物模型）中诱导结膜炎。六只比格犬进行了一项随机、赋形剂对照、平衡交叉试验——在六个不同日期，一只眼睛滴用局部人工泪液（赋形剂），而另一只眼睛滴用六种浓度（0.005 - 500毫克/毫升）组胺溶液中的一种。在滴眼给药后的连续时间点，根据睑结膜和球结膜充血、水肿程度、眼痒及分泌物情况，对每只眼睛给出结膜炎评分。在基线和20分钟时对泪液中的总蛋白含量（TPC）和血清白蛋白进行定量。此外，对13只因各种眼科疾病伴有结膜炎前来就诊的犬进行了检查。局部应用组胺后，实验性诱导的结膜炎迅速发展（<1分钟），持续1 - 3小时（四个最低剂量组）至6 - 8小时（两个最高剂量组）。结膜炎的严重程度呈剂量依赖性。组胺总体耐受性良好，尽管在少数接受≥375毫克/毫升组胺的犬中出现了短暂性睑缘炎、房水闪光和眼压升高。接受≥1.0毫克/毫升组胺的眼睛泪液中TPC和血清白蛋白水平升高，在接受≥375毫克/毫升组胺的眼睛中显著高于赋形剂组和基线水平。13只自然获得性结膜炎犬的泪液中泪腺白蛋白水平也升高，与对侧健康眼睛相比升高了2.7 - 14.9倍。考虑到成本低、非侵入性、自我缓解性质、能够调整疾病持续时间和严重程度以及与自然发生的眼部疾病的共同特征，组胺诱导的结膜炎是眼表转化研究的一个强大模型。1毫克/毫升、10毫克/毫升和375毫克/毫升的组胺溶液分别在犬中诱导轻度、中度和重度结膜炎。结膜炎眼睛泪液中血清白蛋白渗漏表明血 - 泪屏障遭到破坏。
