Expression of extradomain-B-containing fibronectin in subretinal choroidal neovascular membranes

Massimo Nicolò, Attila Birò, Felice Cardillo-Piccolino, Patrizia Castellani, Alfonso Giovannini, Cesare Mariotti, Mario Zingirian, Dario Neri, Luciano Zardi

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7-13
Number of pages7
JournalAmerican Journal of Ophthalmology
Volume135
Issue number1
DOIs
Publication statusPublished - Jan 1 2003

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Fibronectins
Choroidal Neovascularization
Membranes
Immunoconjugates
Photosensitizing Agents
Myopia
Extracellular Matrix
Antibodies
Endothelial Cells
Institutional Practice
Eye Banks
Staining and Labeling
Choroid
Photochemotherapy
Macular Degeneration
von Willebrand Factor
Retina
Protein Isoforms
Immunohistochemistry
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Ophthalmology

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Expression of extradomain-B-containing fibronectin in subretinal choroidal neovascular membranes. / Nicolò, Massimo; Birò, Attila; Cardillo-Piccolino, Felice; Castellani, Patrizia; Giovannini, Alfonso; Mariotti, Cesare; Zingirian, Mario; Neri, Dario; Zardi, Luciano.

In: American Journal of Ophthalmology, Vol. 135, No. 1, 01.01.2003, p. 7-13.

Research output: Contribution to journalArticle

Nicolò, M, Birò, A, Cardillo-Piccolino, F, Castellani, P, Giovannini, A, Mariotti, C, Zingirian, M, Neri, D & Zardi, L 2003, 'Expression of extradomain-B-containing fibronectin in subretinal choroidal neovascular membranes', American Journal of Ophthalmology, vol. 135, no. 1, pp. 7-13. https://doi.org/10.1016/S0002-9394(02)01839-1
Nicolò, Massimo ; Birò, Attila ; Cardillo-Piccolino, Felice ; Castellani, Patrizia ; Giovannini, Alfonso ; Mariotti, Cesare ; Zingirian, Mario ; Neri, Dario ; Zardi, Luciano. / Expression of extradomain-B-containing fibronectin in subretinal choroidal neovascular membranes. In: American Journal of Ophthalmology. 2003 ; Vol. 135, No. 1. pp. 7-13.
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AU - Nicolò, Massimo

AU - Birò, Attila

AU - Cardillo-Piccolino, Felice

AU - Castellani, Patrizia

AU - Giovannini, Alfonso

AU - Mariotti, Cesare

AU - Zingirian, Mario

AU - Neri, Dario

AU - Zardi, Luciano

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N2 - 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.

AB - 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.

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