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Katsuhiko Shinomiya, Mayumi Ueta, Shigeru Kinoshita; The characteristics of a dry-eye mouse model produced by exorbital and intraorbital lacrimal gland excision and histological changes in the ocular surface of that model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):324. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
We previously reported the production of a severe dry-eye mouse model by exorbital lacrimal gland (ELG) and intraorbital lacrimal gland (ILG) excision (Shinomiya et al., ARVO, 2014). The purpose of this present study was to investigate the characteristics of an ELG and ILG excised dry-eye mouse model in detail and to study histological change of the ocular surface in that model in a time-dependent manner.
ELG and ILG excisions were performed unilaterally on 8-week-old female C57BL/6 mice, with sham-surgery performed on the fellow eye. To evaluate dry-eye symptoms, we performed fluorescein staining and measured tear production pre and post surgery. The eyeball and eyelid were enucleated at 4, 8, and 12 weeks post surgery. Tissue sections were then made and subsequently stained with hematoxylin-eosin. The stained sections were then observed by light microscopy to assess the histological change of the ocular surface.
Tear production in the ELG and ILG excised eyes was significantly decreased compared with the sham-surgery control eyes (p<0.0001). Fluorescein staining of the corneal surface revealed severe inflammatory changes such as superficial punctate keratopathy and epithelial defect at 2-weeks post surgery, and persistently at 10-weeks post surgery. Histological examination revealed significant severe changes such as ulceration, inflammatory cell infiltration, and neovascularization in the corneas of the ELG and ILG excised mice at 4-weeks post surgery (p<0.01). Moreover, significant infiltration of inflammatory cells into the mucosal and submucosal layer, as well as epithelial hyperplasia, was observed in the conjunctiva of those mice at 4-weeks post surgery (p<0.001). Those histological changes were advanced at 8-weeks post surgery compared with at 4- and 12-weeks. No significant histological change was observed in the sham-surgery control eyes.
Persistent histological changes were found in the ocular surface of ELG and ILG excised mice, and those changes were most advanced at 8-weeks post surgery. Severe ophthalmological and histological changes were persistently induced, thus indicating that this model is useful for the investigation of tear-volume reduction type dry-eye and for the development of new methods for treating the disease.
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