Phosphatidylserine (PS) is exposed in choroidal neovascular endothelium: PS-targeting antibodies inhibit choroidal angiogenesis in vivo and ex vivo

Tao Li, Bogale Aredo, Kaiyan Zhang, Xin Zhong, Jose S Pulido, Shusheng Wang, Yu Guang He, Xianming Huang, Rolf A. Brekken, Rafael L. Ufret-Vincenty

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

PURPOSE. Choroidal neovascularization (CNV) accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV. METHODS. Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts. RESULTS. We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies led to a 40% to 80% reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis. CONCLUSIONS. We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV.

Original languageEnglish (US)
Pages (from-to)7137-7145
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number12
DOIs
StatePublished - Nov 1 2015

Fingerprint

Choroidal Neovascularization
Phosphatidylserines
Endothelium
Antibodies
Cell Adhesion Molecules
Lasers
Therapeutics
Staining and Labeling
Choroid
Light Coagulation
Macular Degeneration
Inbred C57BL Mouse
Lectins
Vascular Endothelial Growth Factor A
Blood Vessels
Anti-Idiotypic Antibodies

Keywords

  • Choroidal angiogenesis
  • Choroidal neovascularization
  • Choroidal sprouting
  • Phosphatidylserine
  • PS-exposure
  • PS-targeting antibody

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Phosphatidylserine (PS) is exposed in choroidal neovascular endothelium : PS-targeting antibodies inhibit choroidal angiogenesis in vivo and ex vivo. / Li, Tao; Aredo, Bogale; Zhang, Kaiyan; Zhong, Xin; Pulido, Jose S; Wang, Shusheng; He, Yu Guang; Huang, Xianming; Brekken, Rolf A.; Ufret-Vincenty, Rafael L.

In: Investigative Ophthalmology and Visual Science, Vol. 56, No. 12, 01.11.2015, p. 7137-7145.

Research output: Contribution to journalArticle

Li, Tao ; Aredo, Bogale ; Zhang, Kaiyan ; Zhong, Xin ; Pulido, Jose S ; Wang, Shusheng ; He, Yu Guang ; Huang, Xianming ; Brekken, Rolf A. ; Ufret-Vincenty, Rafael L. / Phosphatidylserine (PS) is exposed in choroidal neovascular endothelium : PS-targeting antibodies inhibit choroidal angiogenesis in vivo and ex vivo. In: Investigative Ophthalmology and Visual Science. 2015 ; Vol. 56, No. 12. pp. 7137-7145.
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abstract = "PURPOSE. Choroidal neovascularization (CNV) accounts for 90{\%} of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV. METHODS. Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts. RESULTS. We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies led to a 40{\%} to 80{\%} reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis. CONCLUSIONS. We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV.",
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author = "Tao Li and Bogale Aredo and Kaiyan Zhang and Xin Zhong and Pulido, {Jose S} and Shusheng Wang and He, {Yu Guang} and Xianming Huang and Brekken, {Rolf A.} and Ufret-Vincenty, {Rafael L.}",
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T1 - Phosphatidylserine (PS) is exposed in choroidal neovascular endothelium

T2 - PS-targeting antibodies inhibit choroidal angiogenesis in vivo and ex vivo

AU - Li, Tao

AU - Aredo, Bogale

AU - Zhang, Kaiyan

AU - Zhong, Xin

AU - Pulido, Jose S

AU - Wang, Shusheng

AU - He, Yu Guang

AU - Huang, Xianming

AU - Brekken, Rolf A.

AU - Ufret-Vincenty, Rafael L.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - PURPOSE. Choroidal neovascularization (CNV) accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV. METHODS. Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts. RESULTS. We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies led to a 40% to 80% reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis. CONCLUSIONS. We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV.

AB - PURPOSE. Choroidal neovascularization (CNV) accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV. METHODS. Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts. RESULTS. We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies led to a 40% to 80% reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis. CONCLUSIONS. We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV.

KW - Choroidal angiogenesis

KW - Choroidal neovascularization

KW - Choroidal sprouting

KW - Phosphatidylserine

KW - PS-exposure

KW - PS-targeting antibody

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