Expression of extradomain-B–containing fibronectin in subretinal choroidal neovascular membranes☆☆☆
Accepted 14 August 2002.
Abstract
Purpose
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.
Design
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.
aOphthalmology B Section (M.N., F.C.-P., M.Z.), Department of Neurology and Visual Science, University of Genoa, Genoa, Italy
bLaboratory of Cellular Biology (A.B., P.C., L.Z.), National Institute for Cancer Research, Genoa, Italy
dDepartment of Applied Biosciences (D.N.), Swiss Federal Institute of Technology, Zurich, Switzerland
Inquiries to Luciano Zardi, PhD, Laboratory of Cell Biology, National Institute for Cancer Research, Largo Rosanna Benzi 10, 16132 Genoa, Italy; fax: (+39) 010-352855
☆ This study was performed at the Ophthalmology Clinic, Ancona (surgical excision) and the Laboratory of Cellular Biology, National Institute for Cancer Research, Genoa (immunohistochemistry).
☆☆ This study was supported in part by funds from the Associazione Italiana per la Ricerca sul Cancro (AIRC) and from the European Commission Grant Identification of Novel Markers of Angiogenesis (BIO4-97-2149). Doctor Birò was supported by a postdoctoral fellowship from the International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
ABSTRACT