Tie2 receptor activation for glaucoma

Abstract

This invention relates to the production and genotyping of mice lacking both Angiopoietin 1 and Angiopoietin 2. This invention also relates to the use of Tie2 receptor activation for treatment of open angle glaucoma, congenital glaucoma and cystic kidney disease, and more specifically to the use of angiopoietin 1 recombinant proteins, peptides, VE-PTP phosphatase inhibitors, and Tie2-peptomimetics to improve lymphatic drainage in the Schlemm's canal and corneal limbal lymphatic system for open angle glaucoma and congenital glaucoma patients, and to slow and/or reduce the growth of cysts in patients with cystic kidney disease.

What is claimed is: 
     
         1 . A method of treating a patient having open angle glaucoma, congenital glaucoma or cystic kidney disease comprising administering a pharmaceutical composition comprising agents capable of TIE2 receptor activation. 
     
     
         2 . A method of treating a patient having open angle glaucoma, congenital glaucoma or cystic kidney disease comprising administering a pharmaceutical composition comprising one or more of angiopoietin 1 recombinant proteins, peptides, VE-PTP phosphatase inhibitors, and Tie2-peptomimetics. 
     
     
         3 . The use of a pharmaceutical composition comprising one or more of angiopoietin 1 recombinant proteins, peptides, VE-PTP phosphatase inhibitors and Tie2-peptomimetics for improving ocular lymphatic drainage. 
     
     
         4 . The use of a pharmaceutical composition comprising one or more of angiopoietin 1 recombinant proteins, peptides, VE-PTP phosphatase inhibitors and Tie2-peptomimetics for improving drainage through Schlemm's canal and corneal limbal lymphatics. 
     
     
         5 . A pharmaceutical composition for topical delivery to the eye comprising an effective dosage amount of Tie2 receptor activating agents. 
     
     
         6 . A pharmaceutical composition comprising a pharmaceutically active amount of Tie2 receptor activating agents and a pharmaceutically acceptable carrier for topical delivery to the eye. 
     
     
         7 . The pharmaceutical composition according to  claim 6  wherein the pharmaceutically acceptable carrier is a controlled release vehicle, selected from the group consisting of biocompatible polymers, other polymeric matrices, capsules, microcapsules, nanocapsules, microparticles, nanoparticles, microspheres, bolus preparations, osmotic pumps, diffusion devices, liposomes, lipospheres. 
     
     
         8 . A conditional Angiopoeitin 2 knockout allele. 
     
     
         9 . The use of a conditional Angiopoeitin 2 knockout allele to produce mice lacking Angiopoeitin 2. 
     
     
         10 . The use of the following primers for PCR genotyping of mice: 
       
         
           
                 
                 
               
                     
                   Angpt1Flox, 
                 
                     
                   Forward 
                 
                     
                   5′-CAATGCCAGAGGTTCTTGTGAA-3′; 
                 
                     
                     
                 
                     
                   Reverse 
                 
                     
                   5′-TCAAAGCAACATATCATGTGCA-3′ 
                 
                     
                   (WT: 233 bp product, Angpt1Flox: 328 bp), 
                 
                     
                     
                 
                     
                   Angpt1Delete, 
                 
                     
                   Forward 
                 
                     
                   5′-CAATGCCAGAGGTTCTTGTGAA-3′; 
                 
                     
                     
                 
                     
                   Reverse 
                 
                     
                   5′-TGTGAGCAAAACCCCTTTC-3′ 
                 
                     
                   (431 bp product), 
                 
                     
                     
                 
                     
                   Angpt2Flox, 
                 
                     
                   Forward 
                 
                     
                   5′-GGGAAACCTCAACACTCCAA-3′; 
                 
                     
                     
                 
                     
                   Reverse 
                 
                     
                   5′-ACACCGGCCTCTAGACACAC-3′ 
                 
                     
                   (WT: 224 bp product, Angpt2Flox: 258 bp) 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   Angpt2Delete, 
                 
                     
                   Forward 
                 
                     
                   5′-AAGGCGCATAACGATACCAC-3′; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   Reverse 
                 
                     
                   5′-TGAGAACTCTGCAGCCTTGA-3′ 
                 
                     
                   (Angpt2Flox: 1,372 bp product, Angpt2Delete: 
                 
                     
                   426 bp). 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         11 . A pharmaceutical composition for subcutaneous delivery comprising an effective dosage amount of Tie2 receptor activating agents for treatment of cystic kidney disease. 
     
     
         12 . A pharmaceutical composition comprising a pharmaceutically active amount of Tie2 receptor activating agents and a pharmaceutically acceptable carrier for subcutaneous delivery for treatment of cystic kidney disease.