Methods of compositions for the treatment of ocular diseases

Abstract

Methods and compositions for the treatment of ocular disease with a cyclin dependent kinase inhibitor are provided.

1 . A method for ameliorating proliferative vitreoretinopathy in a mammal, the method comprising administering to an eye of said mammal a nucleotide sequence encoding a p21 cyclin dependent kinase inhibitor, wherein the proliferation of cells in the retinal pigmented epithelium in said eye is reduced so as to ameliorate said proliferative vitreoretinopathy. 
     
     
         2 . The method of  claim 1 , wherein the nucleotide sequence is administered in a viral vector and is expressed in a cell. 
     
     
         3 . The method of  claim 2 , wherein the viral vector is an adenoviral vector. 
     
     
         4 . The method of  claim 3 , wherein the adenoviral vector is a human adenovirus type 5 vector. 
     
     
         5 . The method of  claim 4 , wherein the human adenovirus vector is a replication deficient adenoviral vector. 
     
     
         6 . The method of  claim 5 , wherein the replication deficient vector is deleted in the E4 region. 
     
     
         7 . The method of  claim 6 , wherein the vector retains E4 ORF 6 and E4 ORF 6/7 but does not encode functional E4 peptide. 
     
     
         8 . The method of  claim 1 , wherein the nucleotide sequence is administered to an ophthalmic artery, a subretinal space, a vitreal space, or a subconjunctival space. 
     
     
         9 . The method of  claim 1 , wherein the nucleotide sequence is administered topically. 
     
     
         10 . The method of  claim 9 , wherein the nucleotide sequence is administered in a topical drop formulation. 
     
     
         11 . The method of  claim 1 , wherein the nucleotide sequence is administered in a depot device. 
     
     
         12 . The method of  claim 11 , wherein the depot device comprises a sponge. 
     
     
         13 . The method of  claim 1 , wherein the nucleotide sequence is administered in a non-viral delivery system. 
     
     
         14 . The method of  claim 13 , wherein the nucleotide sequence is administered in a liposome. 
     
     
         15 . The method of  claim 1 , wherein the nucleotide sequence is administered as a naked plasmid. 
     
     
         16 . The method of  claim 1 , wherein said eye of the mammal has a detached retina. 
     
     
         17 . A method for ameliorating proliferative vitreoretinopathy in a mammal, the method comprising administering to an eye of said mammal a p21 cyclin dependent kinase inhibitor, wherein the proliferation of cells in the retinal pigmented epithelium in said eye is reduced so as to ameliorate said proliferative vitreoretinopathy. 
     
     
         18 . The method of  claim 17 , wherein the p21 cyclin dependent kinase inhibitor is administered on a sponge depot. 
     
     
         19 . The method of  claim 17 , wherein said eye of the mammal has a detached retina. 
     
     
         20 . A method for ameliorating age-related macular degeneration in a mammal, the method comprising administering to an eye of said mammal a nucleotide sequence encoding a p21 cyclin dependent kinase inhibitor, wherein the proliferation of cells in said eye is reduced so as to ameliorate said age-related macular degeneration.