Inhibition of corneal inflammation following keratoplasty by birch leaf extract

The objective of this study was to determine the effect of birch leaf (Betula pendula) extract (BPE) on corneal inflammation following keratoplasty in the rat model. T cells were stimulated in vitro in the presence of BPE. Proliferation, activation phenotype and the number of apoptotic/necrotic cells in cell culture were analyzed by flow cytometry. Corneal transplantation was performed between Fisher and Lewis rats. Recipient rats were either treated with cyclosporine A at a low dosage (Low-dose CsA = LDCsA) or received LDCsA in combination with BPE (2 × 1 ml/day). Clinical signs for corneal inflammation and rejection time points were determined. Infiltrating leukocytes were analyzed histologically. BPE specifically inhibited T cell proliferation in vitro by inducing apoptosis. The phenotype was not affected. In vivo, BPE significantly delayed the onset of corneal opacification (p < 0.05). The amount of infiltrating CD45+ leukocytes and CD4+ T cells (p < 0.001) was significantly reduced by BPE, whereas infiltration of CD163+ macrophages was not significantly different between the two groups. BPE selectively induces apoptosis of activated T cells. Accordingly, BPE treatment significantly reduces infiltrating T cells and subsequent corneal opacification following keratoplasty. Our findings suggest BPE as a promising anti-inflammatory drug to treat corneal inflammation.

► Birch leaf extract (BPE) inhibits activated T cells in vitro by specifically inducing apoptosis. ► The phenotype of surviving T cells is not affected in vitro. ► Intraperitoneal injection of BPE has no obvious negative side effects. ► BPE significantly reduces corneal inflammation following keratoplasty clinically and histologically.