Inhibition of corneal inflammation following keratoplasty by birch leaf extract

Exp Eye Res. 2012 Apr;97(1):24-30. doi: 10.1016/j.exer.2012.01.004. Epub 2012 Feb 13.


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 (2×1ml/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.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Betula / chemistry*
  • CD4-Positive T-Lymphocytes / immunology
  • Disease Models, Animal*
  • Female
  • Flow Cytometry
  • Graft Survival / drug effects
  • Graft Survival / immunology
  • Keratitis / immunology
  • Keratitis / prevention & control*
  • Keratoplasty, Penetrating*
  • Leukocyte Common Antigens / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / physiology
  • Phytotherapy*
  • Plant Extracts / therapeutic use*
  • Plant Leaves*
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • Receptors, Cell Surface / metabolism


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Plant Extracts
  • Receptors, Cell Surface
  • Leukocyte Common Antigens
  • Ptprc protein, rat