Objective: To evaluate the efficacy of topical cyclosporine A (CsA) on a penetrating keratoplasty rejection model in rats.
Methods: Lou rats received orthotopic corneal allografts from inbred F344 donors. The rats were treated with one drop of topical solution four times daily for 30 days. Sixty rats were divided into one control (the matrix of CsA solution) and five treatment groups (0.5%, 1.0%, 2.0% CsA, glucocorticoid, glucocorticoid and 1.0% CsA). Rejection index (RI) and mean survival time (MST) were calculated, and histopathological and immunohistopathological examination were performed for each group.
Results: The graft MST was postponed by topical CsA treatment. There was significant difference between each treatment group and the control group (t greater-than-or-equal 2.28, P < 0.0l), especially 2% CsA, steroid and combined 1% CsA and steroid groups, the combined group being the most effective. The RI was lower in all the groups with topical CsA than that in the control group (P < 0.01). The effect of 2% CsA was the same as that of the steroid, while 1% CsA combined steroid was the most effective. The histopathological findings confirmed that the topical application of CsA reduced the inflammatory cells infiltrating the graft stroma and the neovascularization. Immunohistopathological analysis demonstrated that there were fewer CD(+)(11a) T cells and macrophages in the infiltration and intercellular adhesion molecule (ICAM)-1 positive cells in keratocytes and endothelium of grafts in the treatment groups than in the control group.
Conclusions: Topical CsA can inhibit the keratoplasty rejection episodes in the rat and afford better results when combined with topical steroid.