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K. Maruyama, M. Ii, C. Cursiefen, H. Keino, M. Tomita, D. Jackson, R. Dana, J.S. Streilein, D. Losordo, J.W. Streilein; Inflammation Induced Lymphangiogenesis in the Cornea Arises From Innate Immune Cells . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4496.
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Purpose: While the cornea is normally devoid of lymph vessels, lymphangiogenesis does occur in the inflamed cornea. In fact, lymphangiogenesis is a risk factor for graft failure following corneal transplantation. However, the mechanisms that induce new lymph vessels associated with inflammation in the cornea are unknown. The purpose of this study was to determine the type of cell associated with lymphangiogenesis in the inflamed cornea. Methods: Orthotopic corneal transplantation and suture placement were performed in the eyes of BALB/c mice. At various times (3,7, 56 days), following the surgical procedures flat mounts of the corneas were prepared and immune stained (CD31, Cd11b, CD11c and LYVE–1) to identify individual cells associated with the new lymph vessels. Results: As expected, we observed at 3 days, that both blood and lymph vessels emerged simultaneously from the limbal vessels post surgical procedure. To our the surprise the subsequent developmental process of the lymph vessel was different from that observed with the generation of the blood vessel. Whereas the blood vessel arose from the blood vascular endothelial progenitor cells, the lymph vessel was associated with innate immune cell aggregates. Conclusions: The mechanism that lead to lymphangiogenesis in the cornea following an inflammatory insult are different from known mechanism for inflammatory induced angiogenesis. The association of the innate immune cell with the process of corneal lymphangiogenesis reveals a new role for the innate immune cell during corneal inflammation.
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