A new dry eye mouse model produced by exorbital and intraorbital lacrimal gland excision

Katsuhiko Shinomiya,Shigeru Kinoshita,Mayumi Ueta

doi:10.1038/s41598-018-19578-6

Katsuhiko Shinomiya, Shigeru Kinoshita + Show 1 more

Open Access

https://doi.org/10.1038/s41598-018-19578-6

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Abstract

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.

Highlights

Dry eye disease is defined as a chronic and multifactorial disorder of the ocular surface epithelium and its accompanying tear film which results in ocular discomfort and visual impairment[1]
Tear production in the exorbital lacrimal gland (ELG) plus intraorbital lacrimal gland (ILG) excised mice eventually was reduced to 16.6%, 16.2%, 12.4%, and 12.5% of the mean value assessed for sham surgery controls at 2, 4, 8, and 10-weeks after surgery, respectively
We document here that the morphological and physiological changes displayed in our new mouse dry eye model, generated by dual excision of both the ELG and ILG, are more severe than those observed in mice with excision of the ELG only (Figs 2 and 3)

Summary

Introduction

Dry eye disease is defined as a chronic and multifactorial disorder of the ocular surface epithelium and its accompanying tear film which results in ocular discomfort and visual impairment[1]. The ocular dryness and discomfort associated with dry eye disease can progress to visual disturbance and instability of the tear film, potentially leading to damage to the ocular surface. It may have an impact on the ability to work or read and to drive at night[11,12]. For a better understanding of the pathogenesis of, or the molecular mechanisms contributing to, dry eye disease, especially severe aqueous deficiency dry eye caused by SJS/TEN, the appropriate animal model is necessary. We considered that these previously reported animal models for dry eye may not sufficiently mimic severe aqueous deficiency at the ocular surface or may in some cases be problematic to carry out in practice

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