Abstract
Purpose: :
Inflammatory processes in the cornea are sight-threatening. It was shown, that birch leaf extract (BPE) has anti-inflammatory qualities in vitro. An effect of BPE-treatment following corneal transplantation was hypothesized and analyzed alone or in combination with a sub-therapeutic cylosporine A (Low-dose CsA=LDCsA) in the rat model.
Methods: :
T cells or monocytic cells were stimulated in the presence of BPE in vitro. Proliferation, phenotype and number of apoptotic cells were analyzed by flow cytometry. Penetrating keratoplasty was performed between Fisher and Lewis rats. Recipient rats received BPE alone or in combination with LDCsA intraperitoneally. Control animals were either treated with sodium chloride 0.9% or with LDCsA. Clinical signs for inflammation were evaluated and rejection time points were determined. Infiltrating leukocytes were analyzed histologically.
Results: :
BPE selectively inhibited T cell proliferation by inducing apoptosis (p<0.01). No phenotypic changes were observed with respect to CD25- and CD62L-expression. No significant effect of BPE-monotherapy was seen following keratoplasty. Combination of BPE with sub-therapeutic LDCsA significantly delayed onset of corneal opacification and reduced the number of infiltrating CD45+ leukocytes and CD4+ T cells in the graft, whereas the number of infiltrating CD163+ macrophages was comparable.
Conclusions: :
BPE selectively induced apoptosis of activated T cells in vitro. Similarly, number of graft infiltrating T cells and associated corneal opacification were significantly reduced. However, this effect was only achieved if BPE was combined with a sub-therapeutic CsA-dosage. We therefore suggest BPE as an additive treatment following corneal transplantation.
Keywords: inflammation • cornea: basic science • transplantation