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11-1-15/IOVS: “PS-Targeting Mabs [PGN635] Inhibit Choroidal Angiogenesis InVivo & ExVivo” [CNV/MacDegen]
IOVS (Investigative Ophthalmol Visual Sci.) pg.7137-45
UTSW/Mayo/Tulane/PR-China (Brekken/Huang etal)…
Li T1, Aredo B2, Zhang K3, Zhong X2, Pulido JS4, Wang S5, He YG2, Huang X6, Brekken RA7, Ufret-Vincenty RL2
http://www.ncbi.nlm.nih.gov/pubmed/26529048
FULL ARTICLE: http://iovs.arvojournals.org/article.aspx?articleid=2468863
“Phosphatidylserine (PS) Is Exposed in Choroidal Neovascular Endothelium: PS-Targeting Antibodies Inhibit Choroidal Angiogenesis In Vivo and Ex Vivo”
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 [Fully-Human PGN635] 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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OCULAR APPLICATIONS Of PS-TARGETING MABS:
11-1-15/IOVS UTSW/Mayo/Tulane/PRChina: “PS-Targeting Mabs [PGN635] Inhibit Choroidal Angiogenesis InVivo & ExVivo” [CNV/Macular Degen] http://iovs.arvojournals.org/article.aspx?articleid=2468863
5-2012: Two Anti-PS (PGN632 + PGN635) Ocular posters at ARVO'12 Annual Mtg./FtLaud http://tinyurl.com/cax9a4p
..5-6-12/Thorpe+Mayo, "Anti-PS (PGN632 & PGN635) as Potential New Therapy Against Choroidal Neovascularization (CNV) – AMD"
..5-10-12/PPHM+LSU, "Efficacious Clinical Outcome of an Ophthalmic Formulation of PS-binding mab (PGN632) in a Rabbit Model of Acute HSV-1 Keratitis"