Expression of extradomain-B-containing fibronectin in subretinal choroidal neovascular membranes.
OBJECTIVE
To investigate the presence of the fibronectin isoform containing the extradomain B (B-FN), a marker-protein of angiogenesis, in surgically excised human choroidal neovascular membranes (CNVM) to evaluate whether B-FN could be used as a therapeutic target for specific antibody-photosensitizer immunoconjugates.


METHODS
Laboratory investigation.


METHODS
The setting was an institutional practice. The study population consisted of 15 eyes (15 patients) with CNVM undergoing membrane excision (four eyes with age-related macular degeneration, seven with pathologic myopia and four with multifocal choroiditis). The control group consisted of eight eye bank eyes (four subjects) without choroidal neovascularization. Light microscopic immunohistochemistry on cryostat sections of tissues was obtained. B-FN was detected by a human recombinant antibody, CGS-1, and compared with immunostaining for endothelial cells with factor VIII-related antigen. The main outcome measure was the presence of CGS-1 positively stained cells or areas of the extracellular matrix. Staining of CGS-1 was scored on a scale from 0 to 3.


RESULTS
Fourteen of 15 neovascular membranes stained strongly with CGS-1 (score 2 or 3). One membrane from a patient with pathologic myopia was negatively stained (score 0). CGS-1 positive staining was detected around endothelial cells and in the extracellular matrix of CNVMs. The retina of eyes without choroidal neovascularization was negative with CGS-1 in all eight donor eyes, while the choroid contained some weakly CGS-1 positive cells (score 0 and 1, respectively).


CONCLUSIONS
The extradomain B is abundantly expressed in CNVMs, but its expression is more restricted in eyes harboring no apparent choroidal neovascularization. In the future, B-FN might serve as a target for the delivery of antibody-photosensitizer immunoconjugates to newly developed vessels to enhance the selectivity of photodynamic therapy.
Nicolò
Massimo
M
Ophthalmology B Section, Department of Neurology and Visual Science, University of Genoa, Genoa, Italy.
Birò
Attila
A
Cardillo-Piccolino
Felice
F
Castellani
Patrizia
P
Giovannini
Alfonso
A
Mariotti
Cesare
C
Zingirian
Mario
M
Neri
Dario
D
Zardi
Luciano
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002462:Cell Membrane / Q000378:metabolism; D002829:Choroid / Q000378:metabolism; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D002833:Choroiditis / Q000150:complications; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008268:Macular Degeneration / Q000150:complications; D008297:Male; D008875:Middle Aged; D009216:Myopia / Q000150:complications; D020033:Protein Isoforms; D014841:von Willebrand Factor / Q000378:metabolism
D015415:Biomarkers; D005353:Fibronectins; D020033:Protein Isoforms; D014841:von Willebrand Factor