Immunohistochemical localization of vascular endothelial growth factor, transforming growth factor alpha, and transforming growth factor beta1 in human corneas with neovascularization

Cornea. 2000 Jul;19(4):526-33. doi: 10.1097/00003226-200007000-00025.


Purpose: 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.

Conclusion: 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.

Publication types

  • Comparative Study

MeSH terms

  • Antigens, CD / immunology
  • Antigens, Differentiation, Myelomonocytic / immunology
  • CD3 Complex / immunology
  • Cornea / immunology
  • Cornea / metabolism*
  • Cornea / pathology
  • Corneal Neovascularization / metabolism*
  • Corneal Neovascularization / pathology
  • Corneal Neovascularization / surgery
  • Corneal Transplantation
  • Endothelial Growth Factors / immunology
  • Endothelial Growth Factors / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Lymphokines / immunology
  • Lymphokines / metabolism*
  • Macrophages / immunology
  • Retrospective Studies
  • T-Lymphocytes / immunology
  • Transforming Growth Factor alpha / immunology
  • Transforming Growth Factor alpha / metabolism*
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism*
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD3 Complex
  • CD68 antigen, human
  • Endothelial Growth Factors
  • Lymphokines
  • Transforming Growth Factor alpha
  • Transforming Growth Factor beta
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors