Expression of growth factors in the conjunctiva from patients with active trachoma.
OBJECTIVE
The blinding complications of trachoma are associated with progressive conjunctival fibrosis due to excessive accumulation of extracellular matrix (ECM) components. We studied the processes involved in the regulation of fibrosis in trachoma by investigating the expression of the fibrogenic and angiogenic connective tissue growth factor (CTGF) and basic fibroblast growth factor (bFGF), the angiogenic vascular endothelial growth factor (VEGF), the angiogenesis-associated endothelial cell marker CD105 (endoglin), and the ECM protein tenascin in the conjunctiva.


METHODS
Conjunctival biopsy specimens from six patients with active trachoma, and six control subjects were studied by immunohistochemical techniques using monoclonal and polyclonal antibodies directed against CTGF, bFGF, VEGF, CD105, and tenascin.


RESULTS
In the normal conjunctiva, weak immunoreactivity for VEGF was observed in epithelial cells. There was no immunoreactivity for the other antibodies. In all trachoma specimens, immunoreactivity for CTGF and bFGF was localized in monocytes/macrophages, positive for the CD68 marker. Strong immunoreactivity for VEGF was observed in epithelial cells and on vascular endothelial cells. CD105 immunoreactivity was observed on vascular endothelial cells. Immunoreactivity for tenascin was noted in the upper substantia propria.


CONCLUSIONS
These findings suggest that macrophages play an active role in conjunctival scarring, upregulated local production of CTGF, bFGF, and VEGF contributes to both fibrous tissue growth and angiogenesis, vascular endothelial cells are activated and are undergoing active angiogenesis, and deposition of tenascin reflect remodelling of the conjunctiva in trachomatous conjunctivitis.
Abu El-Asrar
A M
AM
Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa
Al-Kharashi
S A
SA
Missotten
L
L
Geboes
K
K
D000293:Adolescent; D015703:Antigens, CD / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003228:Conjunctiva / Q000098:blood supply / Q000378:metabolism*; D055513:Connective Tissue Growth Factor; D000071063:Endoglin; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D019063:Tenascin / Q000378:metabolism; D014141:Trachoma / Q000276:immunology / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D015703:Antigens, CD; C526317:CCN2 protein, human; C064206:ENG protein, human; D000071063:Endoglin; D006133:Growth Substances; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011956:Receptors, Cell Surface; D019063:Tenascin; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D055513:Connective Tissue Growth Factor