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N. J. Cutrufello, Y. Tan, C. A. Medina-Mendez, R. E. Martinez, J. Echegaray, V. L. Perez; Role of T Cell Recruitment and Endogenous Endostatin Production in Corneal Allograft Rejection. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1552.
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Previously we showed that administration of exogenous endostatin increases survival of corneal allografts. This suggests that this antiangiogenic factor plays an important role in the survival of corneal allografts. In this work we further investigate the relationship of endostatin and immune responses in corneal transplantation
Orthotopic complete MHC mismatched corneal allotransplants (C57BL/6 →Balb/c) and syngenic transplants (Balb/c →Balb/c) were performed. Clinical scores were done at days 0, 1, 3, 7, 10, 20, & 40 after surgery and at similar time points eyes were frozen, sectioned and corneal protein lystates were prepared. Endostatin production was assessed by Enzyme Linked Immunosorbent Assay (ELISA) and recruitment of T-cells was quantified by immunohistochemistry.
Endostatin was present in both allogenic and syngeneic corneal grafts at post operative day (POD) 0, and steadily increased and peaked at POD10 . In syngeneic grafts, the levels of endostatin remained elevated through POD40. In contrast, allogeneic grafts, had a significantly decreased production of endostatin. Graft survival correlated with endostatin production. Rejection of allogeneic grafts began after the decreased production of endostatin on POD10, while syngeneic graft survival was 100%. The decrease in endostatinin corneal allografts also correlated with the increase influx of T-cells into the graft.
Our data suggests that endostatin is produced after corneal transplantation as a potential mechanism to prevent neovascularization and graft failure. The fact that a decreased endostatin production is observed in only rejected corneal allograft infiltrated by T cells, suggests a close relationship between immunity and neovascularization. We propose a novel hypothesis that alloimmune recognition and immune responses are the first critical step in the regulation of angiogensis in corneal allotransplation.
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