Immunohistochemical localization of vascular endothelial growth factor, transforming growth factor alpha, and transforming growth factor beta1 in human corneas with neovascularization.
OBJECTIVE
To analyze presence and distribution of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)alpha, and TGFbeta1 in human corneas with neovascularization due to different corneal diseases.


METHODS
Indirect immunohistochemistry for VEGF, TGFalpha, and TGFbeta1, was performed on paraffin-embedded corneas obtained by keratoplasty. Corneas from each of the four main groups of histopathologic diagnoses associated with corneal neovascularization were analyzed (scarring after keratitis, graft rejection/insufficiency, acute necrotizing keratitis, scarring after mechanical/chemical injury). Subclassification of inflammatory infiltrates was done using immunohistochemistry for CD3 (T-lymphocytes) and CD68 (macrophages).


RESULTS
The analyzed angiogenic factors were detectable in corneas from all four histopathologic groups in a similar distribution; capillary endothelial cells, stromal and intravascular inflammatory cells (T-lymphocytes, macrophages), and basal corneal epithelial cells stained positive for the tested angiogenic factors.


CONCLUSIONS
The angiogenic factors VEGF, TGFalpha, and TGFbeta1 are detectable in human corneas with neovascularization. Their distribution is quite uniform in different corneal diseases, resulting in corneal angiogenesis. An antiangiogenic therapy inhibiting corneal neovascularization by antagonizing angiogenic factors would have to counteract several angiogenic factors.
Department of Ophthalmology, Friedrich-Alexander-University Erlangen-Nürnberg, Germany. claus.cursiefen@augen.med.uni-erlange.d
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Cursiefen
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Rummelt
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Küchle
D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D003315:Cornea / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016510:Corneal Neovascularization / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D016039:Corneal Transplantation; D016228:Endothelial Growth Factors / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008222:Lymphokines / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology; D016211:Transforming Growth Factor alpha / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D017252:CD3 Complex; D016228:Endothelial Growth Factors; D008222:Lymphokines; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C067980:CD68 antigen, human; D000097382:CD68 Molecule