Materials and methods for treating ocular-related disorders

Abstract

The present invention is directed to a method of prophylactically or therapeutically treating an animal for at least one ocular-related disorder, e.g., ocular neovascularization or age-related macular degeneration. The method comprises contacting an ocular cell with an expression vector comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and the same or different nucleic acid sequence encoding a neurotrophic agent. The method also can comprise contacting an ocular cell with different expression vectors, each comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and/or a nucleic acid sequence encoding a neurotrophic agent. In addition, the present invention provides a viral vector comprising a nucleic acid sequence encoding pigment epithelium-derived factor (PEDF) or a therapeutic fragment thereof.

What is claimed is:  
     
         1 . A method of prophylactically or therapeutically treating an animal for an ocular-related disorder, wherein the method comprises contacting an ocular cell with 
 (a) an expression vector comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and the same or different nucleic acid sequence encoding a neurotrophic agent, or    (b) different expression vectors, each comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and/or a nucleic acid sequence encoding a neurotrophic agent, 
 such that the nucleic acid sequence encoding the inhibitor of angiogenesis and/or the nucleic acid sequence encoding the neurotrophic agent are expressed, thereby resulting in the production of the inhibitor of angiogenesis and the neurotrophic agent to prophylactically or therapeutically treat the animal for an ocular-related disorder.  
   
     
     
         2 . The method of  claim 1 , wherein the method comprises contacting the ocular cell with an expression vector comprising the nucleic acid sequence encoding the inhibitor of angiogenesis and the nucleic acid sequence encoding the neurotrophic agent.  
     
     
         3 . The method of  claim 2 , wherein the nucleic acid sequence encoding the inhibitor of angiogenesis and the nucleic acid sequence encoding the neurotrophic agent are the same nucleic acid sequence.  
     
     
         4 . The method of  claim 1 , wherein the method comprises contacting the ocular cell with at least two different types of expression vectors, wherein each expression vector comprises a nucleic acid sequence encoding an inhibitor of angiogenesis and/or a nucleic acid sequence encoding a neurotrophic factor.  
     
     
         5 . The method of  claim 1 , wherein the ocular-related disorder is ocular neovascularization.  
     
     
         6 . The method of  claim 5 , wherein the ocular neovascularization is neovascularization of the choroid.  
     
     
         7 . The method of  claim 5 , wherein the ocular neovascularization is neovascularization of the retina.  
     
     
         8 . The method of  claim 7 , wherein the neovascularization of the retina is associated with diabetic retinopathy.  
     
     
         9 . The method of  claim 1 , wherein the ocular-related disorder is age-related macular degeneration.  
     
     
         10 . The method of  claim 1 , wherein at least one expression vector is an adeno-associated vector.  
     
     
         11 . The method of  claim 1 , wherein at least one expression vector is an adenoviral vector.  
     
     
         12 . The method of  claim 11 , wherein at least one expression vector is an adenoviral vector and at least one expression vector is an adeno-associated viral vector.  
     
     
         13 . The method of  claim 11 , wherein the adenoviral vector is replication deficient.  
     
     
         14 . The method of  claim 1 , wherein the expression vector(s) is (are) administered to cells of neural origin, ciliary epithelial cells, retinal pigment epithelial cells, glial cells, fibroblasts, endothelial cells, or cells of the trabecular meshwork.  
     
     
         15 . The method of  claim 1 , wherein the expression vector(s) is (are) administered to iris epithelial cells, corneal cells, ciliary epithelial cells, Mueller cells, or astrocytes.  
     
     
         16 . The method of  claim 1 , wherein the expression vector(s) is (are) administered to a patient greater than 55 years of age.  
     
     
         17 . The method of  claim 1 , wherein the expression vector(s) is (are) administered to an area of vascular leakage.  
     
     
         18 . The method of  claim 1 , wherein the expression vector(s) is present in or on a device that allows controlled release of the expression vector(s).  
     
     
         19 . The method of  claim 1 , wherein the expression vector(s) is (are) administered topically, subconjunctivally, retrobulbarly, periocularly, subretinally, suprachoroidally, or intraocularly.  
     
     
         20 . The method of  claim 4 , wherein at least one expression vector comprises the nucleic acid sequence encoding an inhibitor of angiogenesis.  
     
     
         21 . The method of  claim 1 , wherein the inhibitor of angiogenesis is selected from the group consisting of an anti-angiogenic factor, an anti-sense molecule specific for an angiogenic factor, a ribozyme, and a receptor for an angiogenic factor.  
     
     
         22 . The method of  claim 1 , wherein the nucleic acid sequence encoding the inhibitor of angiogenesis encodes multiple inhibitors of angiogenesis.  
     
     
         23 . The method of  claim 4 , wherein at least one expression vector comprises the nucleic acid sequence encoding a neurotrophic factor.  
     
     
         24 . The method of  claim 4 , wherein at least one expression vector comprises the nucleic acid sequence encoding an inhibitor of angiogenesis and the nucleic acid sequence encoding a neurotrophic agent.  
     
     
         25 . The method of  claim 4 , wherein the inhibitor of angiogenesis and the neurotrophic agent are a single factor.  
     
     
         26 . The method of  claim 1 , wherein the neurotrophic agent is pigment epithelial-derived factor.  
     
     
         27 . The method of  claim 1 , wherein the method comprises administering the expression vector(s) in two or more applications to the same eye of the animal.