Methods of using gap junctions as therapeutic targets for the treatment of degenerative disorders of the retina

Abstract

The disclosure provides methods of treating a condition of the retina by administering an inhibitor of connexin 36 and/or an inhibitor of connexin 45 to a subject with a retinal condition. This disclosure further provides compositions for the treatment of a retinal condition which include an inhibitor of connexin 36 and/or an inhibitor of connexin 45.

What is claimed is: 
     
         1 . A method of treating a condition of the retina comprising administering an inhibitor of connexin 36 and/or an inhibitor of connexin 45 to a subject in need thereof. 
     
     
         2 . The method of  claim 1 , comprising administration of both an inhibitor of connexin 36 and an inhibitor of connexin 45. 
     
     
         3 . The method of  claim 1  or  2  wherein said condition of the retina is selected from glaucoma, macular degeneration, retinitis pigmentosa, diabetic retinopathy and retinal ischemia. 
     
     
         4 . The method of any of  claims 1 - 3  wherein said inhibitor or inhibitors is selected from an antisense polynucleotide directed to connexin 36 mRNA, an antisense polynucleotide directed to connexin 45 mRNA, and combinations thereof. 
     
     
         5 . The method of  claim 4  wherein said antisense polynucleotide selectively binds the sequence of SEQ ID NO: 1 or SEQ ID NO: 2. 
     
     
         6 . The method of any of  claims 3 - 5  wherein the antisense polynucleotide is complementary to all of or a portion of connexin 36 mRNA and/or connexin 45 mRNA. 
     
     
         7 . The method of  claim 7  wherein said antisense polynucleotide is the exact complement of all or a portion of connexin 36 mRNA and/or connexin 45 mRNA. 
     
     
         8 . The method of any of  claims 1 - 7  wherein said antisense polynucleotides hybridize to connexin 36 mRNA and/or connexin 45 mRNA with a melting temperature of greater than 20° C., 30° C. or 40° C. under physiological conditions. 
     
     
         9 . The method of any of  claims 1 - 3  wherein said inhibitor is a small molecule inhibitor. 
     
     
         10 . The method of  claim 9  wherein said small molecule inhibitor is selected from 18-Beta-glycyrrhetinic acid (18Beta-GA) and meclofenamic acid (MFA). 
     
     
         11 . The method of any of  claims 1 - 10 , comprising repeat administration of said inhibitor or inhibitors for a period of 1 week to 1 year. 
     
     
         12 . The method of any of  claims 1 - 11 , wherein said administration is topical administration or intraocular injection. 
     
     
         13 . A pharmaceutical composition for treatment of a retinal condition comprising an inhibitor of connexin 36 and/or an inhibitor of connexin 45. 
     
     
         14 . The composition of  claim 13 , wherein said composition comprises an inhibitor of connexin 36 and an inhibitor of connexin 45. 
     
     
         15 . The composition of  claim 13  or  14 , wherein said inhibitor or inhibitors are selected from an antisense molecule directed to connexin 36 mRNA, an antisense molecule directed to connexin 45 mRNA, and combinations thereof. 
     
     
         16 . The composition of  claim 13  or  14 , wherein said composition comprises a small molecule inhibitor of connexin 36 and/or a small molecule inhibitor of connexin 45. 
     
     
         17 . The composition of any of  claims 13 - 16 , formulated for topical administration to the eye. 
     
     
         18 . Use of the composition of any of  claims 13 - 17  in the treatment of a condition of the retina. 
     
     
         19 . Use according to  claim 18 , wherein the condition of the retina is selected from glaucoma, macular degeneration, retinitis pigmentosa, diabetic retinopathy and retinal ischemia.