Immunopathogenesis of conjunctival remodelling in vernal keratoconjunctivitis.
OBJECTIVE
To study the processes involved in mediating conjunctival remodelling in vernal keratoconjunctivitis (VKC) by investigating the expression of integrin receptors, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), transforming growth factor-beta(TGF-beta), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and Ki67 antigen, which is a marker for cell proliferation.


METHODS
Conjunctival biopsy specimens from 16 patients with active VKC and nine control subjects were studied by immunohistochemical techniques using monoclonal and polyclonal antibodies directed against the integrin alpha3 and alpha6 subunits, EGFR, VEGF, TGF-beta, bFGF, PDGF, and Ki67 antigen. The phenotype of inflammatory cells expressing growth factors was examined by double immunohistochemistry.


RESULTS
In the normal conjunctiva, very weak immunoreactivity was observed for EGFR and VEGF in epithelial cells, and for alpha3 and alpha6 integrin subunits on basal epithelial cells, and on vascular endothelial cells in the upper substantia propria. There was no immunoreactivity for the other antibodies. In VKC specimens, strong staining for alpha3 and alpha6 integrin subunits was observed on the membranes of basal and suprabasal epithelial cells, and all vascular endothelial cells. Immunoreactivity for Ki67 antigen was observed in the nuclei of the basal and suprabasal epithelial cells. Strong immunoreactivity was observed for EGFR in the deeper layers of the epithelium, and for VEGF in all epithelial cells. Inflammatory cells expressing EGFR, VEGF, TGF-beta, bFGF, and PDGF were noted in 8, 9, 11, 10, and 10 specimens, respectively. The majority of inflammatory cells expressing growth factors were eosinophils (45+/-4%) and monocytes/macrophages (35+/-4%).


CONCLUSIONS
Chronic conjunctival inflammation in VKC is associated with increased staining of alpha3, and alpha6 integrin subunits, EGFR, VEGF, TGF-beta, bFGF, and PDGF that might mediate conjunctival remodelling.
Abu El-Asrar
A M
AM
Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. abuasrar@KSU.edu.sa
Al-Mansouri
S
S
Tabbara
K F
KF
Missotten
L
L
Geboes
K
K
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002648:Child; D003228:Conjunctiva / Q000737:chemistry* / Q000473:pathology; D003233:Conjunctivitis, Allergic / Q000276:immunology* / Q000473:pathology; D004804:Eosinophils / Q000737:chemistry; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D039422:Integrin alpha3 / Q000032:analysis; D039503:Integrin alpha6 / Q000032:analysis; D016023:Integrins / Q000032:analysis*; D019394:Ki-67 Antigen / Q000032:analysis; D008264:Macrophages / Q000737:chemistry; D008297:Male; D009000:Monocytes / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D017978:Receptors, Growth Factor / Q000032:analysis*; D016212:Transforming Growth Factor beta / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D015415:Biomarkers; D039422:Integrin alpha3; D039503:Integrin alpha6; D016023:Integrins; D019394:Ki-67 Antigen; D010982:Platelet-Derived Growth Factor; D017978:Receptors, Growth Factor; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D066246:ErbB Receptors