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Impressum
Contribution of lymphatic drainage system in corneal allograft rejection in mice
1Hoffmann F., 1Zhang E. P., 1Mueller A., 1Schulte F., 2Foss H. D., 2Coupland S.
1Augenklinik, 2Institut für Pathologie, UKBF, Freie Universität Berlin
Objective: To modulate aqueous outflow via the uveoscleral pathway
and to determine its influence on corneal graft survival in mice.
Methods: BALB/c mice received corneal transplants from C3H mice
and were placed randomly in three treatment groups: saline, pilocarpine
or latanoprost. Three further groups received adjuvant systemic and topical
corticosteroid treatment. Infiltrating lymphocytes, neutrophils and macrophages
in the transplants were investigated using immunoperoxidase staining on
postoperative days 3, 5, 7, 9, 11 and 13 in an additional 96 animals.
Ipsilateral and contralateral submandibular lymph nodes were weighed and
investigated for cytokine expression using in-situ hybridization. Tracer
experiments were conducted using 99mTC colloidal albumin Nanocoll. The
count rate was determined in the submandibular lymph nodes, the spleen
and the blood following both subconjunctival and intracameral injection.
Results: Pilocarpine and latanoprost had no influence on aqueous
outflow in BALB/c mice and did not influence allograft survival. Gr1+
neutrophils and F4/80+ macrophages were dominant amongst the infiltrating
cells three days postoperative. Between the postoperative days 3 and 13,
a greater increase in lymphocytes compared to other cell groups was observed.
Following allogeneic transplantation, 1% of lymphocytes in the ipsilateral
submandibular lymph node were positive for the Th1 cytokine IFN-g. Calculations
of accumulated Nanocoll in the lymph nodes and spleen after intracameral
injection revealed a 16% aqueous outflow via the uveoscleral routes. Subconjunctival
injection of Nanocoll lead to an increase in flow (97%) to the submandibular
lymph nodes.
Conclusion: Our data confirm the existence of functional lymphatic
drainage via the uveoscleral pathway and conjunctiva in the mouse. Further,
cells within the lymph node respond to stimuli upstream and this reaction
can be therapeutically manipulated. Promotion of aqueous outflow via the
major route by occlusion of the uveoscleral pathway may improve the acceptance
of corneal transplants in man.