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Kelly K Nichols, Samuel D Hanlon, Jason J Nichols; A Murine Model for Characterizing Glandular Changes in Obstructive Meibomian Gland Dysfunction. Invest. Ophthalmol. Vis. Sci. 2014;55(13):14.
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© ARVO (1962-2015); The Authors (2016-present)
Obstructive meibomian gland dysfunction is a leading cause of dry eye disease among clinical patients. More research is needed to fully understand the histopathological factors contributing to clinically observable meibomian gland dropout. Previous animal models have employed the application of toxic chemicals or genetically modified strains, both of which may have secondary effects beyond simple glandular obstruction. The purpose of the present study was to develop a murine model of MGD by physical blockage of the gland orifices and to characterize subsequent morphological and histological changes in the glands and meibocytes.
Using a stereo microscope, meibomian gland orifices of anesthetized mice were cauterized with a modified small vessel cauterizer. At 1 hour, 1, 4, 8, and 12 weeks post-treatment, external images of the eyelids were obtained, after which the mice were euthanized, the eyelids removed, pinned down on a paraffin dissecting tray and meibomian glands imaged from reverse. Thereafter the eyelids were processed for histological sections. Thin sections were cut with an ultramicrotome and stained with toluidine blue and examined with a light microscope. Electron micrograph grids were prepared and stained with lead citrate and uranyl acetate. In selected cases, contents from obstructed glands were removed by incision and mild compression. Age-matched control mice were processed in similar fashion for each of the time points.
Twenty-four hours after cauterization, external examination of the eyelids showed no overt signs of inflammation. At one week after cauterization there were no visible surface connections for the meibomian glands to release their contents, but otherwise the meibomian glands appeared relatively normal. There was progressive change through the 12 weeks post cautery, ranging from mild ductal engorgement to large cyst formation, and profound glandular dropout. Incision of distended glands produced solidified “cheesy” material.
Obstruction of the meibomian gland orifices produced stasis of the meibum which ultimately induced alterations in the morphology of the glands and glandular dropout characteristic of clinical MGD. This animal model may be used for investigating therapeutic agents for treatment of evaporative dry eye disease and for exacerbating factors.
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