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B. Walcott, L.C. Moore, A. Birzgalis, P.R. Brink; Gender Related Differences in Innervation and Secretion of the Lacrimal Glands of NOD Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2509.
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Purpose Non-Obese Diabetic mice (NOD) show many of the symptoms of Sjögren’s Syndrome with extensive lymphocytic infiltrations of the salivary and lacrimal glands. Unlike the human disease, however, the most extensive infiltrates are seen in male and not female NOD mice. We wanted to compare the innervation and function of glands from both male and female NOD mice of different ages. Methods Exorbital lacrimal glands were removed from NOD male and female mice at different ages. After fixation in 4% paraformaldehyde they were sectioned and treated with antisera against synaptophysin, a neural marker. For fluid flow measurements, the gland was exposed in anesthetized mice and the duct inserted into a pipette. For patch-clamp and volume measurements, cells were isolated from glands and plated on matrigel covered plates. Results In young (1-2 month) NOD mice, the female glands showed extensive synaptophysin-like immunoreactivity and no lymphocytic infiltrates. Male glands at the same age had significantly less synaptophysin immunoreactivity with some areas of the lobes showing little to no innervation. Even at 1-2 months of age, male glands showed some lymphocytic infiltrates. At 3 months of age, male glands showed significant infiltrates and less innervation while female glands were unchanged. Young (1-2 month) male glands showed 60% less fluid flow on topical carbachol stimulation than control glands (C57 males). Cells isolated from these glands showed less of a volume reduction on stimulation than was seen in control cells when exposed to carbachol. Whole cell patch-clamp also showed that these cells had a 50% reduction in the passive IV currents when compared to control cells. Conclusions Young (1-2 month old) NOD male mice have a reduced innervation density and reduced fluid flow that suggests that the characteristics of the disease process begin early and before there is extensive lymphocytic infiltration. The change in the passive electrical properties suggests that there are significant alterations in ion channel function that may contribute to the reduced fluid flow in this dry eye model animal.
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