A New Rabbit Model of Chronic Dry Eye Disease Induced by Complete Surgical Dacryoadenectomy
A New Rabbit Model of Chronic Dry Eye Disease Induced by Complete Surgical Dacryoadenectomy
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DOI：
10.1080/02713683.2019.1594933
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发表时间：
2019-04-14
影响因子：
2
通讯作者：
Rigas, Basil
中科院分区：
文献类型：
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作者：
Honkanen, Robert;Huang, Wei;Rigas, Basil
目的/目标：干眼症（DED）是一种常见且治疗效果不佳的疾病，需要新型动物模型来了解其病理生理学，并评估新药物治疗的疗效和其他参数。迄今为止描述的超过10种DED兔模型具有显著的局限性，包括诱导轻度疾病，缺乏一致性，以及当化学试剂用于疾病诱导时的脱靶效应。我们的目标是开发一种新的兔慢性DED模型，克服现有模型的局限性。材料与方法：我们对正常成年新西兰白色兔的所有眼眶泪腺（LGs;泪腺切除术）进行了完整的手术切除。去除瞬膜后一周，我们手术切除眶上级LG，然后切除眼睑上级LG，最后切除下LG。手术在麻醉下进行，每只眼需要约1小时，耐受性良好。结果如下：泪腺切除术诱导严重DED，表现为泪液破裂时间试验减少>90%，Schirmer泪液试验减少50%，泪液渗透压增加10%，虎红染色评分显著增加。DED在8周的观察期内持续存在，基本上没有变化。假手术兔没有显示出这样的变化，除了泪膜破裂时间测试中的非显著和短暂的减少，这是对眼部手术的反应。结论：这种稳定的、慢性的、主要是缺水的DED的模型概括了人DED的关键临床和组织学特征，并且适合于研究眼表面稳态、DED的病理生理学以及用于DED治疗的候选药物的功效。
Purpose/Aim: Dry eye disease (DED), common and suboptimally treated, is in need of novel animal models to understand its pathophysiology and assess the efficacy and other parameters of new pharmacological agents for its treatment. The more than 10 rabbit models of DED described to date have significant limitations including induction of mild disease, lack of consistency, and off-target effects when chemical agents are used for disease induction. Our aim was to develop a new model of chronic DED in rabbits that overcomes the limitations of existing models. Materials and Methods: We performed a complete surgical resection of all orbital lacrimal glands (LGs; dacryoadenectomy) in normal adult New Zealand White rabbits. One week after removal of the nictitating membrane, we surgically removed the orbital superior LG, followed by removal of the palpebral superior LG, and finally removal of the inferior LG. Surgery was performed under anesthesia, required about 1 h/eye, and was well-tolerated. Results: Dacryoadenectomy induced severe DED, evidenced by >90% reduction in the tear break up time test, 50% reduction in the Schirmer tear test, 10% increase in tear osmolarity, and a marked increase in the rose bengal staining score. DED was sustained and essentially unchanged for the eight weeks of observation. Sham-operated rabbits showed no such changes, with the exception of a non-significant and transient reduction in the tear break up time test, a response to ocular surgery. Conclusions: This model of stable, chronic, predominantly aqueous-deficient DED recapitulates key clinical and histological features of human DED and is suitable for the study of ocular surface homeostasis, of the pathophysiology of DED, and of the efficacy of candidate drugs for DED treatment.