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K. Maruyama, D.W. Losordo, P.A. D'Amore; Lymphangiogenesis In A Diabetic Murine Model . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1631.
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Impaired wound healing is a common and debilitating complication of diabetes. It is well established that normal wound healing involves the recruitment of inflammatory cells, such as macrophages, and the formation of new blood vessels (hemangiogenesis) however the role of lymphangiogenesis has not been well studied. We investigated the effect of diabetes on wound healing–associated lymphangiogenesis in murine corneal suture model.
Male diabetic mice (C57BKS db/db) and control (db/+) (8–10 wk) were used. Using stromal incisions that encompassed more than 120 degrees of the corneal circumference, three 11–0 nylon sutures were placed intrastromally. Seven days after suture placement, the mice were euthanized and the corneas collected, then stained with LYVE–1 (lymphatic endothelium marker), CD31 (pan endothelial marker) and CD11b (macrophage marker). Digital pictures of the flat mounts were taken using a Spot Image Analysis System, and the area covered by blood– and lymphatic vessels positive for CD31 or LYVE–1, respectively, was quantified using NIH Image software.
: Lymphangiogenesis and hemangiogenesis, as measured by quantification of LYVE–1 positive lymphatic vessels and CD31–positive blood vessels in the cornea seven days after suture placement, were equivalent in wild type and db/+ mouse corneas. However, both lymphangiogenesis and hemangiogenesis were significantly suppressed in the diabetic mice (p< 0.02) as compared to control (db/+) mice. Moreover, the number of macrophages that had infiltrated into the cornea was reduced in db/db mouse relative to the db/+ mice. Similarly, quantification of thioglycollate–induced macrophages in the peritoneal cavity of db/db mice revealed significantly less than in db/+ mice (p=0.02).
Diabetes leads to reduced blood vessel and lymphatic growth during the inflammation associated with corneal wound healing. We speculate that the impaired wound healing process associated with diabetes may be due, at least in part, to the reduced macrophage infiltration and resultant attenuated angiogenesis and lymphangiogenesis.
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