Methods for treating eye disorders

摘要

The present invention relates to compositions and methods for inhibiting loss of a retinal ganglion cell in a subject, comprising non-invasively applying to the surface of the eye of the subject an ophthalmic composition comprising a therapeutically effective amount of at least one siRNA which down regulates expression of a target gene associated with loss of the retinal ganglion cell, thereby inhibiting loss of the retinal ganglion cell in the subject. The methods of the invention also relate to the use of chemically modified siRNA compounds possessing structural motifs which down-regulate the expression of human genes expressed in retinal tissue in the mammalian eye.

主权项

1. A method of treating a patient suffering, or at risk of suffering, from an ocular disease, an ocular disorder or an ocular injury, comprising administering to the patient a therapeutically effective amount of a double-stranded oligonucleotide having the structure:(sense strand; SEQ ID NO: 9015)5′ iB-GCCAGAAUGUGGAACUCCU 3′(antisense strand; SEQ ID NO: 9516)3′ CGGUCUUACACCUUGAGGA 5′ wherein each of A, C, U and G is a nucleotide and each consecutive nucleotide is joined to the next nucleotide by a phosphodiester bond; wherein the sense strand comprises, counting from the 5′ terminus, an unmodified ribonucleotide at each of positions 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 and 19, a L-deoxycytidine at position 18, and an inverted deoxyabasic moiety (iB) covalently attached at the 5′ terminus; and wherein the antisense strand comprises, counting from the 5′ terminus, a 2′-O-Methyl sugar-modified ribonucleotide at each of positions 2, 4, 6, 8, 11, 13, 15, 17 and 19 and an unmodified ribonucleotide at positions 1, 3, 5, 7, 9, 10, 12, 14, 16 and 18; or a pharmaceutically acceptable salt of such double-stranded oligonucleotide; and a pharmaceutically acceptable carrier.