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Hyung Keun Lee, Eun Ju Chang, Mee-Kum Kim, Soon Won Hong, Eung-Kweon Kim; Expression Of Lymphangiogenic Markers In Rejected Human Corneal Bed After Penetrating Keratoplasty. Invest. Ophthalmol. Vis. Sci. 2011;52(14):371.
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To investigate the mechanism of lymphangiogenesis in graft rejection process, we determined the expression level of several lymphangiogenic markers in rejected human corneal bed through immunohistochemical and molecular biologic works.
Seventeen recipient corneas were secured from the patients who performed re-keratoplasty for graft rejection after penetrating keratoplasty. All corneas showed signs of active rejection such as Khodadoust line before re-keratoplasty. The corneas were cut in half to make two pieces of the same size and one piece was used for immunostaining and the other was used for RT-PCR for each corneas. To determine the lymphangiogenic markers, expression of vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D, VEGFR-2, VEGFR-3, fibroblast growth factor-2 (FGF-2), and LYVE-1 were investigated. Two normal corneas were included as control.
From the immunostaining of LYVE-1, we found many LYVE-1 expressed cells in anterior and posterior stroma and lymphatic vessels growing into the paracentral cornea. The expressions of VEGF-A, VEGFR-2, and LYVE-1 were upregulated in rejected cornea compared to the normal. In contrast, expressions of VEGF-C, VEGF-D, and VEGFR-3 were not changed in rejected graft. By the quantitative real time RT-PCR data, mRNA for VEGF-A, VEGFR2 expression ratio (keratoplastic cornea/normal cornea) was 8.2 in VEGF-A, 3.9 in VEGFR2. However, mRNA for VEGF-C, VEGF-D, and VEGF3 were 1.3, 0.9, and 1.2, respectively. FGF-2 did not show the increment in rejected corneal bed.
These findings may suggest that VEGF-A and VEGFR2 axis is more important pathway for corneal graft rejection and lymphangiogenesis than VEGF-C, -D, or VEGFR3 axis.
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