Graefe's Arch Clin Exp Ophthalmol(1996) 234:116-124 © Springer-Verlag 1996 Sarah E. Coupland Lothar Krause Friedrich Hoffmann The influence of penetrating keratoplasty and cyclosporin A therapy on MHC class II (la)-positive cells in the rat iris and choroid Received: 16 August 1994 Revised version received: 6 April 1995 Accepted: 4 May 1995 S.E. Coupland • L. Krause - F. Hoffmann Augenabteilung, Universit~itsklinikum Benjamin Franklin, Hindenburgdamm30, D- 12200 Berlin, Germany S.E. Coupland (~) Institut far Pathologie, Universitfitsklinikum Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany Tel.: +49-30-8445-4233/2295 Abstract • Background: The pres- ence of Ia-positive cells (MHC class II equivalent) has been previ- ously reported in the iris and cho- roid of various species. They have been reported to have both round and dendritic morphologies; the lat- ter may represent classic dendritic cells, potent antigen-presenting cells (APCs). It is possible that the dendritic-like cells play a important role in (auto)immune processes of uveal and other ocular tissues. Us- ing the flat or whole mount tech- nique, the distribution of Ia-positive cells in the rat iris and choroid was investigated following penetrating keratoplasty (PKP) and following treatment with cyclosporin A (CsA). • Methods: Lewis (LW) rats received corneal buttons from Lewis-Brown Norway (LW-BN) donors and were randomly assigned to the following groups: (i) operat- ed, untreated (n=24); (ii) operated, CsA-treated (10 mg/kg i.m.; n=22). Controls were groups (iii) normal LW rats (n= 13); (iv) uuop- erated, CsA-treated (16 days' treat- ment; n= 8); (v) anterior perforation of the anterior chamber (n=3); (vi) eight corneal sutures only (n=4); (vii) syngeneic operated (LW to LW; n=4). Animals of groups (i) and (ii) were killed on the 5th, 9th and 13th postoperative days and on appearance of the corneal rejection (group i, day 13; group ii, day 16). Both eyes were enucleated, imme- diately fixed, and iris-choroid flat mounts were examined for Ia-posi- tive cells using APAAP immunohis- tochemistry. • Results: In the nor- mal Lewis rat iris, scattered Ia-pos- itive cells of both nondendritic and dendritic morphology were ob- served. CsA treatment in the unop- erated rat did not result in a signifi- cant decrease in the percentage of dendritic cells in the iris or cho- roid. Anterior chamber perforation, the placement of sutures in the cornea and syngeneic PKP resulted in a moderate increase in iris Ia- positive cells. Allogeneic transplan- tation resulted in a large increase in both types of Ia-positive cells, par- ticularly on day 13 with corneal re- jection. In group ii, an initial de- crease in Ia-positive cells until day 13 was observed; upon rejection (day 16), the histological picture was similar to that of untreated animals. Alterations in the operated choroid were also apparent following CsA treatment. • Conclusion: Corneal transplantation in the Lewis rat re- sults in an increase in Ia-positive cells in the iris; CsA therapy can delay but not prevent this reaction. Changes in choroidal Ia-positive cells following PKP were not ap- parent, their numbers being affect- ed only by CsA treatment follow- ing grafting. Introduction The major histocompatibility complex (MHC) refers to a region of highly polymorphic genes on the short arm of chromosome 6 in man (chromosome 17 in rodents), which are responsible for the coding of human leucocyte antigens (HLA) located on the surface of a variety of cells. The MHC system is responsible for a variety of biological functions, including determination of the sus- ceptibility of individuals to autoimmune disorders and of allograft survival [32].