VEGF-A as an inhibitor of angiogenesis and methods of using same
AssigneeUniversity of Kentucky Research Foundation
InventorJayakrishna Ambati
Life of this patent
Estimating the term…
Abstract
The invention relates to methods and compositions for the treatment or prevention of ocular angiogenesis and neovascularization associated with neovascular disease. Administration of vascular endothelial growth factor (VEGF)-A into the eye when macrophage infiltration is reduced inhibits ocular angiogenesis.
Claims45
A composition for inhibiting ocular angiogenesis comprising an effective amount of VEGF-A, PLGF-1, PLGF-2, or a combination thereof, that induces VEGF-A interaction with VEGFR-1.
A method for inhibiting ocular angiogenesis, comprising administering after ocular injury to at least one eye of a subject in need thereof a therapeutically effective amount of a composition comprising VEGF-A, PLGF-1, PLGF-2 or a combination thereof and a pharmaceutically acceptable carrier.
The method of using VEGF-A, PLGF-1, PLGF-2 or a combination thereof to inhibit angiogenesis comprising administering to at least one eye of a subject in need thereof a therapeutically effective amount of a composition comprising VEGF-A, PLGF-1, PLGF-2 or a combination thereof, and a pharmaceutical carrier, after injury but prior to macrophage recruitment.
A composition for inhibiting ocular angiogenesis comprising an effective amount of VEGF-A, PLGF-1, PLGF-2 or a combination thereof that induces VEGF-A, PLGF-1 and/or PLGF-2 interacting with VEGFR-1.
A method for preventing ocular neovascularization, comprising administering to at least one eye of a subject in need thereof a therapeutically effective amount of a composition comprising VEGF-A, PLGF-1, PLGF-2 or a combination thereof and a pharmaceutically acceptable carrier, after ocular injury but prior to macrophage recruitment.
The method of using VEGF-A, PLGF-1, PLGF-2 or a combination thereof to treat and/or prevent ocular neovascularization comprising administering to the eye of a subject in need thereof a therapeutically effective amount of a composition comprising VEGF-A, PLGF-1, PLGF-2 or a combination thereof, and a pharmaceutical carrier after injury but prior to macrophage recruitment.
A method of inhibiting ocular angiogenesis by inducing VEGFR-1 activity comprising administering to at least one eye of a patient in need thereof a composition comprising an effective amount of a SPARC antagonist that inhibits SPARC inactivation of VEGFR-1.
A method for treating or preventing ocular neovascularization by inducing VEGFR-1 activity comprising administering to at least one eye of a patient in need thereof a composition comprising an effective amount of a SPARC antagonist that inhibits SPARC inactivation of VEGFR-1.
A method for identifying a modulator of SPARC interacting with VEGFR-1 comprising the steps of:
- (a) measuring interaction between SPARC and VEGFR-1 in the presence and absence of a test compound under conditions that allow SPARC to inhibit VEGFR-1;
- and
- (b) identifying as a modulator a test compound which alters SPARC inhibition of VEGFR-1.
A composition for treatment or prevention of ocular neovascularization comprising an effective amount of a SPARC antagonist and a pharmaceutically acceptable carrier.
(canceled)
A method for determining a course of treatment for ocular neovascularization comprises measuring the amount of SPARC in an eye of a subject in need thereof, comprising the steps of:
- (a) introducing into the vitreous of an eye an antibody conjugated to a fluorescent label that binds to SPARC;
- (b) measuring the amount of fluorescence in the eye;
- and
- (c) determining the course of treatment based on the results,
- wherein a low or reduced level of SPARC is indicative that VEGF-A, PLGF-1 and/or PLGF-2 would be principally routed through VEGFR-1, and a high or increased level of SPARC is indicative that VEGF-A, PLGF-1 and/or PLGF-2 would be principally routed through VEGFR-2.
A method for determining a course of treatment for ocular neovascularization comprising measuring the amount of SPARC in an eye of a subject in need thereof, comprising the steps of:
- (a) taking a sample of vitreous or subretinal fluid from an eye of a subject in need thereof;
- (b) introducing into the sample an antibody conjugated to a fluorescent label that binds to SPARC;
- and
- (c) measuring the amount of fluorescence in the sample,
- wherein a low or reduced level of SPARC is indicative that VEGF-A, PLGF-1 and/or PLGF-2 would be principally routed through VEGFR-1, and a high or increased level of SPARC is indicative that VEGF-A, PLGF-1 and/or PLGF-2 would be principally routed through VEGFR-2.
A method for determining a course of treatment for ocular neovascularization comprising measuring the amount of SPARC in the choroids or RPE of an eye of a subject in need thereof, comprising the steps of:
- (a) introducing into the eye an antibody conjugated to a fluorescent label that binds to SPARC;
- and
- (b) imaging the eye for the fluorescent signal by angiography.
Dependencies are inferred from the claim text.