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.

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 adenoviral vector comprising a nucleic acid sequence encoding a receptor for an angiogenic factor, and a different nucleic acid sequence encoding a neurotrophic agent, wherein the adenoviral vector is replication-deficient as a result of a deletion comprising the adenoviral E1 region and a deletion comprising a portion of the adenoviral E4 region, and wherein the adenoviral vector optionally lacks all or part of the adenoviral E3 region, or   (b) a first adenoviral vector comprising a nucleic acid sequence encoding a receptor for an angiogenic factor and a second adenoviral vector comprising a nucleic acid sequence encoding a neurotrophic agent, wherein the first and second adenoviral vectors are different, and wherein the first and second adenoviral vectors are replication-deficient as a result of a deletion comprising the adenoviral E1 region and a deletion comprising a portion of the adenoviral E4 region, and wherein the first and second adenoviral vectors optionally lack all or part of the adenoviral E3 region,   such that the nucleic acid sequence encoding the receptor for an angiogenic factor and the nucleic acid sequence encoding the neurotrophic agent are expressed, thereby resulting in the production of the receptor for an angiogenic factor 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 adenoviral vector comprising the nucleic acid sequence encoding the receptor for an angiogenic factor and the nucleic acid sequence encoding the neurotrophic agent. 
   
   
       3 . The method of  claim 1 , wherein the method comprises contacting the ocular cell with a first adenoviral vector comprising a nucleic acid sequence encoding a receptor for an angiogenic factor and a second adenoviral vector comprising a nucleic acid sequence encoding a neurotrophic agent, wherein the first and second adenoviral vectors are different. 
   
   
       4 . The method of  claim 1 , wherein the receptor for an angiogenic factor is a Flt receptor. 
   
   
       5 . The method of  claim 1 , wherein the neurotrophic agent is pigment epithelial-derived factor (PEDF). 
   
   
       6 . The method of  claim 1 , wherein the ocular-related disorder is ocular neovascularization. 
   
   
       7 . The method of  claim 6 , wherein the ocular neovascularization is neovascularization of the choroid. 
   
   
       8 . The method of  claim 6 , wherein the ocular neovascularization is neovascularization of the retina. 
   
   
       9 . The method of  claim 8 , wherein the neovascularization of the retina is associated with diabetic retinopathy. 
   
   
       10 . The method of  claim 1 , wherein the ocular-related disorder is age-related macular degeneration. 
   
   
       11 . The method of  claim 1 , wherein the adenoviral 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. 
   
   
       12 . The method of  claim 1 , wherein the adenoviral vector(s) is (are) administered to iris epithelial cells, corneal cells, ciliary epithelial cells, Mueller cells, or astrocytes. 
   
   
       13 . The method of  claim 1 , wherein the adenoviral vector(s) is (are) administered to a patient greater than 55 years of age. 
   
   
       14 . The method of  claim 1 , wherein the adenoviral vector(s) is (are) administered to an area of vascular leakage. 
   
   
       15 . The method of  claim 1 , wherein the adenoviral vector(s) is (are) present in or on a device that allows controlled release of the adenoviral vector(s). 
   
   
       16 . The method of  claim 1 , wherein the adenoviral vector(s) is (are) administered topically, subconjunctivally, retrobulbarly, periocularly, subretinally, suprachoroidally, or intraocularly. 
   
   
       17 . The method of  claim 1 , wherein the method comprises administering the adenoviral vector(s) in two or more applications to the same eye of the animal. 
   
   
       18 . The method of  claim 1 , wherein the method comprises administering to the animal about 10 6  adenoviral particles to about 10 12  adenoviral particles.