Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Pharmacology Group, Non-Clinical Research, Global R&D Division, Santen Pharmaceutical Co., Ltd., Ikoma, Japan.
Sci Rep. 2018 Jan 24;8(1):1483. doi: 10.1038/s41598-018-19578-6.
Chronic dry eye is an increasingly prevalent condition worldwide, with resulting loss of visual function and quality of life. Relevant, repeatable, and stable animal models of dry eye are still needed. We have developed an improved surgical mouse model for dry eye based on severe aqueous fluid deficiency, by excising both the exorbital and intraorbital lacrimal glands (ELG and ILG, respectively) of mice. After ELG plus ILG excision, dry eye symptoms were evaluated using fluorescein infiltration observation, tear production measurement, and histological evaluation of ocular surface. Tear production in the model mice was significantly decreased compared with the controls. The corneal fluorescein infiltration score of the model mice was also significantly increased compared with the controls. Histological examination revealed significant severe inflammatory changes in the cornea, conjunctiva or meibomian glands of the model mice after surgery. In the observation of LysM-eGFP mice tissues, postsurgical infiltration of green fluorescent neutrophils was observed in the ocular surface tissues. We theorize that the inflammatory changes on the ocular surface of this model were induced secondarily by persistent severe tear reduction. The mouse model will be useful for investigations of both pathophysiology as well as new therapies for tear-volume-reduction type dry eye.
慢性干眼病是一种在全球范围内日益流行的疾病,会导致视力功能和生活质量下降。目前仍需要相关的、可重复的、稳定的干眼病动物模型。我们通过切除小鼠的外眶和内眶泪腺(ELG 和 ILG),开发了一种基于严重水样液缺乏的改良手术性干眼病小鼠模型。在切除 ELG 加 ILG 后,通过荧光素渗透观察、泪液生成测量和眼表组织学评估来评估干眼病症状。与对照组相比,模型小鼠的泪液生成明显减少。与对照组相比,模型小鼠的角膜荧光素渗透评分也显著增加。组织学检查显示,手术后模型小鼠的角膜、结膜或睑板腺有明显的严重炎症改变。在 LysM-eGFP 小鼠组织的观察中,术后观察到眼表组织中绿色荧光中性粒细胞的浸润。我们推测,这种模型眼表的炎症变化是由持续严重的泪液减少继发引起的。该小鼠模型将有助于研究泪液减少型干眼病的病理生理学和新疗法。