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Local or short‐term systemic costimulatory molecule blockade prolongs rat corneal allograft survival
Author(s) -
Thiel Michael A,
Steiger Jurg U,
O'Connell Philip J,
Lehnert Anne M,
Coster Douglas J,
Williams Keryn A
Publication year - 2005
Publication title -
clinical and experimental ophthalmology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.3
H-Index - 74
eISSN - 1442-9071
pISSN - 1442-6404
DOI - 10.1111/j.1442-9071.2005.00974.x
Subject(s) - medicine , systemic administration , blockade , cd28 , monoclonal antibody , corneal transplantation , antibody , fusion protein , immunology , perioperative , corneal graft , pharmacology , surgery , ophthalmology , cornea , immune system , receptor , t cell , biology , biochemistry , microbiology and biotechnology , in vivo , gene , recombinant dna
Background: Costimulatory molecule blockade with antibody‐based immunosuppressive agents has been shown to prolong the survival of many types of allograft. The effects were evaluated of local costimulatory molecule blockade with different CTLA4‐Ig constructs and of systemic, short‐term treatment with an anti‐CD28 monoclonal antibody on orthotopic corneal allograft survival in the rat. Methods: Adult Fischer‐344 rats underwent Wistar‐Furth orthotopic corneal grafts. The rats were treated with two different CTLA4‐fusion proteins administered intraocularly in the perioperative period, or systemically with anti‐CD28 monoclonal antibody JJ319. Corneal graft survival was determined by daily slit‐lamp examination. The day of rejection was defined as the first postoperative day on which the iris margin was no longer clearly visible through the corneal graft. Results: Local administration of CTLA4‐fusion protein with mutated immunoglobulin constant region domains via a single perioperative intraocular injection prolonged corneal graft survival modestly but significantly ( P < 0.05), in contrast to a CTLA4‐fusion protein with wild‐type immunoglobulin domains, which had no effect on graft survival ( P > 0.5). Systemic short‐term administration of 400 µg total of an anti‐CD28 monoclonal antibody also prolonged corneal graft survival significantly ( P < 0.05) and was more effective than systemic administration of 2 mg total of CTLA4‐fusion protein ( P < 0.05). Conclusions: Local administration of CTLA4‐fusion protein with mutated (non‐functional) immunoglobulin domains or systemic administration of anti‐CD28 monoclonal antibody can prolong corneal allograft survival in the rat.