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David A Sullivan, Ferran Jardi, XIAOMIN CHEN, Huatao Xie, Frank Claessens, Yang Liu; Influence of androgen receptor absence on murine lacrimal and meibomian glands.. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4918.
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Androgens exert a significant impact on the structure and/or function of the lacrimal (LG) and meibomian (MG) glands. Androgen deficiency, in turn, is a significant risk factor for LG and MG dysfunction and aqueous-deficient and evaporative dry eye disease (DED). Androgen actions appear to be mediated primarily through androgen receptors (ARs) in epithelial cell nuclei. We hypothesize that the AR knockout (ARKO) mouse, which has no AR, will serve as a very relevant model for LG and MG dysfunction and DED. Our goal was to begin to test this hypothesis.
We examined the LGs and lower MGs from young adult (9-13 weeks old) ARKO (n = 11/group) and age-matched wildtype (WT; n = 9/group) male mice. These tissues were fixed in 4% paraformaldehyde and 10% sucrose overnight and processed for histological evaluation. We analyzed multiple sections (6 µm; stained with H&E and PAS) of MG tissues with a Nikon eclipse E800 microscope at 100x and 200x magnification. We quantified MG acinar areas (excluding ducts and interstitial tissues) by using ImageJ. We examined LGs for the extent of inflammation by multiplying the number of infiltrates/section by the total amount of infiltrate/section (each infiltrate graded from “0” [no infiltrate] to 4.0 [largest infiltrate], then summed).
Our results demonstrate that the acinar areas of ARKO MGs are significantly smaller (i.e. 40% less) than those of WT controls. The ARKO MGs also showed evidence of thickened ducts and secretory acini inserting into duct walls. These ductal features, as well as the reduced acinar area, are characteristic of MG dysfunction. Our findings also show that the LGs of ARKO mice are significantly smaller (i.e. ~ ¼ the size) than those of WT controls. In addition, the ARKO LGs contain a significant amount of inflammation, at levels almost 3-fold greater/section than found in LGs of WT controls. Given the disparity in LG sizes, this would indicate that ARKO LGs contain at least an order of magnitude more inflammation per mg LG than the WT controls.
Overall, our results support our hypothesis and indicate that ARKO mice may be a very relevant model for LG and MG dysfunction and, quite possibly, the associated DED.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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