METHODS OF USING GAP JUNCTIONS AS THERAPEUTIC TARGETS FOR THE TREATMENT OF DEGENERATIVE DISORDERS OF THE RETINA
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.
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.