SDF1-alpha is associated with VEGFR-2 in human choroidal neovascularisation.
Endothelial progenitor cells (EPCs) have been shown to contribute to experimentally induced choroidal neovascularisation (CNV) in animal models. The recruitment pathway for EPCs is dependent on the chemokine stromal cell derived factor 1-alpha (SDF) and its receptor CXCR4 on the progenitor cell. We examined 23 specimens of CNV occurring secondary to a variety of aetiologies (10 secondary to age-related macular degeneration (AMD), 4 inflammatory, 4 idiopathic and 5 melanoma-associated) for the presence and distribution of SDF and CXCR4 in order to determine if this pathway may play a role in neovascularisation. Specimens were examined by immunohistochemistry using a panel of antibodies against SDF, CXCR4, vascular endothelial growth factor receptor 2 (VEGFR-2), CD34 (endothelial cells), CD68 (macrophages) and cytokeratins (retinal pigment epithelium; RPE). SDF was detected in 2 cases of CNV in AMD, 1 inflammatory CNV, 3 idiopathic CNVs and in 3 cases of CNV associated with melanoma. A significant association was found between SDF and VEGFR-2 immunostaining in individual membranes (p<0.001). Localisation of SDF immunostaining to the presumed RPE was also significant (p<0.05). CXCR4 immunostaining was widespread in all membranes in keeping with the published work of other investigators. Our study suggests that SDF, which may be produced by the RPE, could play a role in CNV.
Guerin
Eoin
E
Unit of Ophthalmology, Department of Clinical Sciences, UCD, Duncan Building, University of Liverpool, Daulby Street, Liverpool, L69 3GA, United Kingdom. eoinguerin@gmail.com
Sheridan
Carl
C
Assheton
David
D
Kent
David
D
Wong
David
D
Grant
Maria
M
Hiscott
Paul
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002648:Child; D002830:Choroid Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000473:pathology; D002833:Choroiditis / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007633:Keratins / Q000378:metabolism; D008268:Macular Degeneration / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008297:Male; D008545:Melanoma / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D019718:Receptors, CXCR4 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D015703:Antigens, CD; D015415:Biomarkers; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D007633:Keratins; D040301:Vascular Endothelial Growth Factor Receptor-2