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.

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 . The method of  claim 1 , wherein the agent is selected from one or more angiopoietin 1 recombinant proteins, peptides, VE-PTP phosphatase inhibitors, and Tie2-peptomimetics. 
     
     
         3 . A method for improving ocular lymphatic drainage in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising one or more of angiopoietin 1 recombinant proteins, peptides, VE-PTP phosphatase inhibitors and/or Tie2-peptomimetics. 
     
     
         4 . The method of  claim 3 , wherein ocular lymphatic drainage through Schlemm's canal and corneal limbal lymphatics is improved. 
     
     
         5 . (canceled) 
     
     
         6 . A pharmaceutical composition comprising a pharmaceutically active amount of one or more 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 . (canceled) 
     
     
         9 . (canceled) 
     
     
         10 . The use of the following primers for PCR genotyping of mice: TABLE-US-00001 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 . (canceled) 
     
     
         12 . A pharmaceutical composition comprising a pharmaceutically active amount of one or more Tie2 receptor activating agents and a pharmaceutically acceptable carrier for subcutaneous delivery for treatment of cystic kidney disease.