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D. Zoukhri, E. R. Macari, C. L. Kublin; Mechanisms of Murine Lacrimal Gland Repair Following Experimentally Induced Inflammation. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1915.
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To determine if murine lacrimal gland is capable of self-repair following experimentally induced inflammation and if so, determine the mechanisms involved in this process.
Inflammation was induced by direct injection of recombinant human interleukin-1α (IL-1α, 1 µg in 2 µl) into the exorbital lacrimal glands of anesthetized female BALB/c mice. Animals were sacrificed 1, 2, 3, 4, or 7 days following the injection. Before sacrifice, the amount of tears was measured using phenol red-impregnated cotton threads. The exorbital lacrimal glands were then removed and processed for measurement of protein secretion, histology, immunohistochemistry and western blotting.
Compared to saline injected BALB/c mice, the amount of tears was significantly reduced following IL-1α injection at 1, 2, and 3 days. Tear production returned to normal 7 days post IL-1α injection. Similarly, compared to control, protein secretion was inhibited by 91%, 67%, and 33% at 1, 2, and 3 days post IL-1α injection, respectively, but returned to normal at 7 days. Concomitant with these changes, the lacrimal gland underwent a severe inflammatory response at 1, 2, and 3 days during which the number of apoptotic (TUNEL positive) acinar cells increased and the amount of Bcl-2 (an anti-apoptotic protein) decreased. Between 3 and 7 days following IL-1α injection, the lacrimal gland underwent of phase of repair during which the number of Ki67 (a marker of cell proliferation) and nestin (a marker of progenitor/stem cells) positive cells increased. During the repair phase, the TGFß/Smad signaling pathway was activated.
We conclude from these studies that the murine lacrimal gland is capable of self-repair following experimentally induced inflammation. Our results also suggest that the lacrimal gland contain progenitor stem/cells, which might actively participate in tissue repair.
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