Contribution of lymphatic drainage system in corneal allograft rejection in mice.
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 corticosteroids. The kinetics of infiltrating lymphocytes, neutrophils and macrophages in the transplants was investigated in an additional 96 animals. Cytokine expression in the submandibular lymph nodes and spleen was investigated using in-situ hybridization and RNAse protection assay. Tracer experiments were conducted using 99mTC colloidal albumin Nanocoll; count rates were determined in the submandibular lymph nodes, spleen and blood following both subconjunctival and intracameral injection.


RESULTS
Neither pilocarpine nor latanoprost had any influence on aqueous outflow or allograft survival in mice. Neutrophils and macrophages dominated the infiltrating cells 11 days postoperative in both treated and untreated grafts. On postoperative day 13, a greater increase in lymphocytes than in other cell groups was observed in allogeneic grafts. Following allogeneic transplantation, 1% of lymphocytes in ipsilateral submandibular lymph nodes were positive for IFN-gamma. Tracer studies revealed a 16% aqueous outflow via the uveoscleral routes following intracameral injection of Nanocoll; this was increased by 97% with subconjunctival injection.


CONCLUSIONS
Our data confirm the existence of functional lymphatic drainage via the uveoscleral pathway and conjunctiva in the mouse. Cells within the ipsilateral submandibular lymph node respond to stimuli upstream. This reaction could potentially be manipulated to improve graft survival.
Hoffmann
F
F
Department of Ophthalmology, University Hospital Benjamin Franklin, Free University Berlin, Germany. fhoffman@zedat.fu-berlin.de
Zhang
E P
EP
Mueller
A
A
Schulte
F
F
Foss
H D
HD
Franke
J
J
Coupland
S E
SE
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D002465:Cell Movement; D016039:Corneal Transplantation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D000077338:Latanoprost; D008198:Lymph Nodes / Q000502:physiology*; D008214:Lymphocytes / Q000502:physiology; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000502:physiology; D010862:Pilocarpine / Q000494:pharmacology; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D012590:Sclera / Q000187:drug effects / Q000378:metabolism; D014184:Transplantation, Homologous; D014602:Uvea / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D011461:Prostaglandins F, Synthetic; D010862:Pilocarpine; D000077338:Latanoprost