title: Inhibition of corneal inflammation following keratoplasty by birch leaf extract.
abstract: 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.
authors.affiliation: University Eye Hospital Freiburg, Killianstr. 5, 79106 Freiburg, Germany. Katrin.Wacker@uniklinik-freiburg.de
authors.forename: Katrin
authors.initials: K
authors.lastname: Wacker
authors.forename: Carsten
authors.initials: C
authors.lastname: Gründemann
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kern
authors.forename: Laura
authors.initials: L
authors.lastname: Bredow
authors.forename: Roman
authors.initials: R
authors.lastname: Huber
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinhard
authors.forename: Johannes
authors.initials: J
authors.lastname: Schwartzkopff
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D029662:Betula / Q000737:chemistry*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology; D007634:Keratitis / Q000276:immunology / Q000517:prevention & control*; D015948:Keratoplasty, Penetrating; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D018515:Plant Leaves; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011956:Receptors, Cell Surface / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D010936:Plant Extracts; D011956:Receptors, Cell Surface; D017493:Leukocyte Common Antigens; C516771:Ptprc protein, rat