RNAi therapy for treatment and/or prevention of glaucoma
The present invention is directed to an RNAi-inducing agent capable of reducing and/or inhibiting the expression of proteins associated with the tight junction complex joining Schlemm's canal endothelial cells (SCEC) in the eye of a subject for use in the prevention and/or treatment of glaucoma. Specifically, the RNAi-inducing agent is capable of reducing and/or inhibiting the expression of proteins expressed in the tight junction complex or supporting the tight junction complex joining Schlemm's canal endothelial cells (SCEC) in the eye of a subject for use in the prevention and/or treatment of glaucoma. Methods using this RNAi-inducing agent are also contemplated.
1. A method for the treatment of glaucoma in a subject comprising the step of administering an effective amount of an RNAi inducing agent capable of reducing the expression of one or more tight junction proteins expressed in the tight junction complex joining Schlemm's canal endothelial cells (SCEC) in an eye of the subject, wherein the RNAi inducing agent is selected from the group consisting of an RNAi agent, a nucleic acid vector encoding an RNAi agent, and a virus carrying a nucleic acid vector encoding an RNAi agent; and wherein the RNAi inducing agent is capable of reducing the expression of one or more tight junction proteins selected from the group consisting of claudin-11, Tricellulin and ZO-1.
2. The method of claim 1 , wherein the RNAi inducing agent is selected from the group consisting of siRNA, shRNA and an RNAi-inducing vector whose presence within a cell results in production of an siRNA or shRNA.
3. The method of claim 1 , wherein the glaucoma is a primary or secondary glaucoma.
4. The method of claim 1 , wherein the RNAi inducing agent is administered locally to the eye.
5. The method of claim 1 , wherein the RNAi inducing agent is administered by intracameral injection or inoculation.
6. The method of claim 1 , wherein the RNAi inducing agent is administered episclerally into the aqueous humour outflow tissues.
7. The method of claim 1 wherein the subject is resistant or non-responsive to conventional pressure lowering medications.
8. The method according to claim 1 , wherein said administration of said RNAi inducing agent reduces intra-ocular pressure in said eye of said subject.
9. The method of claim 3 , wherein the primary glaucoma is primary open-angle glaucoma (POAG).
10. The method of claim 1 , wherein the RNAi inducing agent is administered by viral mediated delivery.
11. The method according to claim 1 , wherein said administration of said RNAi inducing agent reduces ocular hypertension in said eye of said subject.
12. The method according to claim 1 , wherein said administration of said RNAi inducing agent results in the reversible and transient RNAi-mediated suppression of the tight junction complex joining Schlemm's canal endothelial cells.