RNAi-mediated inhibition of frizzled related protein-1 for treatment of glaucoma

1. A method of attenuating expression of Frizzled Related Protein-1 mRNA of a subject, comprising:

administering to an eye of the subject a composition comprising an effective amount of interfering RNA and a pharmaceutically acceptable carrier, the interfering RNA comprising:

a sense nucleotide strand, an antisense nucleotide strand, and a region of at least near- perfect contiguous complementarity of at least 19 nucleotides;

wherein the sense strand is 19 to 21 nucleotides and comprises a nucleic acid sequence of SEQ ID NO: 18 wherein the thymines are replaced with uracils, wherein the expression of Frizzled Related Protein-1 mRNA is attenuated thereby.

2. The method of claim 1 wherein the subject is a human and the human has glaucoma.

3. The method of claim 1 wherein the subject is a human and the human is at risk of developing glaucoma.

4. The method of claim 1 further comprising administering to the subject a second interfering RNA having a length of 19 to 49 nucleotides and comprising:

a sense nucleotide strand, an antisense nucleotide strand, and a region of at least near- perfect complementarity of at least 19 nucleotides;

wherein the antisense strand of the second interfering RNA hybridizes under physiological conditions to a second portion of mRNA corresponding to SEQ ID NO:1 or SEQ ID NO:191, and the antisense strand has a region of at least near-perfect contiguous complementarity of at least 19 nucleotides with the second hybridizing portion of mRNA corresponding to SEQ ID NO:1 or SEQ ID NO:191, respectively.

5. The method of claim 1 wherein the sense nucleotide strand and the antisense nucleotide strand are connected by a loop nucleotide strand.

6. The method of claim 1 wherein the composition is administered via a topical, intravitreal, transcleral, periocular, conjunctival, subtenon, intracameral, subretinal, subconjunctival, retrobulbar, intracanalicular, or suprachoroidal route.

7. The method of claim 1 wherein the interfering RNA is administered via in vivo expression from an expression vector capable of expressing the interfering RNA.

8. A method of treating glaucoma in a subject in need thereof, comprising:

administering to an eye of the subject a composition comprising an effective amount of interfering RNA, and a pharmaceutically acceptable carrier, the interfering RNA comprising a sense nucleotide strand, an antisense nucleotide strand, and a region of at least near-perfect contiguous complementarity of at least 19 nucleotides;

wherein the sense strand is 19 to 21 nucleotides and comprises a nucleic acid sequence of SEQ ID NO: 18 wherein the thymines are replaced with uracils,

wherein the glaucoma is treated thereby.

9. The method of claim 8 wherein the subject is a human and the human has glaucoma.

10. The method of claim 8 wherein the subject is a human and the human is at risk of developing glaucoma.

11. The method of claim further comprising administering to the subject a second interfering RNA having a length of 19 to 49 nucleotides and comprising:

a sense nucleotide strand, an antisense nucleotide strand, and a region of at least near- perfect complementarity of at least 19 nucleotides;

wherein the antisense strand of the second interfering RNA hybridizes under physiological conditions to a second portion of mRNA corresponding to SEQ ID NO:1 or SEQ ID NO:191, and the antisense strand has a region of at least near-perfect contiguous complementarity of at least 19 nucleotides with the second hybridizing portion of mRNA corresponding to SEQ ID NO:1 or SEQ ID NO:191, respectively.

12. The method of claim 8 wherein the sense nucleotide strand and the antisense nucleotide strand are connected by a loop nucleotide strand.

13. The method of claim 8 wherein the composition is administered via a topical, intravitreal, transcleral, periocular, conjunctival, subtenon, intracameral, subretinal, subconjunctival, retrobulbar, intracanalicular or suprachoroidal route.

14. The method of claim 8 wherein the interfering RNA is administered via in vivo expression from an expression vector capable of expressing the interfering RNA.

15. The method of claim 1 wherein the composition is administered via ocular injection.

16. The method of claim 15 wherein the composition is administered via a topical, intravitreal, transcleral, periocular, conjunctival, subtenon, intracameral, subretinal, subconjunctival, retrobulbar, intracanalicular, or suprachoroidal route.

17. The method of claim 8 wherein the composition is administered via ocular injection.

18. The method of claim 17 wherein the composition is administered via a topical, intravitreal, transcleral, periocular, conjunctival, subtenon, intracameral, subretinal, subconjunctival, retrobulbar, intracanalicular, or suprachoroidal route.