Bone morphogenic proteins (bmp),bmp receptors and bmp binding proteins and their use in the diagnosis and treatment of glaucoma
The present invention provides methods and kits for diagnosing and treating glaucoma.
1 . A method for diagnosing glaucoma in a sample obtained from a cell or bodily fluid by detecting altered expression of a bone morphogenic family member gene, said method comprising the steps of:
g) obtaining a tissue or fluid sample from a patient suspected of having glaucoma;
h) extracting DNA from said sample;
i) obtaining a plurality of PCR primers, wherein said primers each comprise a sequence consisting of from 18 to 1547 contiguous nucleotides from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, or SEQ ID NO:53;
j) amplifying regions of the extracted DNA using said primers to obtain a PCR product;
k) resolving the PCR product; and
l) identifying differences between the sequence of the amplified extracted DNA and the sequence of the primer;
where a difference between the amplified sequence and the primer is diagnostic of glaucoma.
2 . The method of claim 1 , wherein said tissue or fluid sample is blood or buccal cells.
3 . The method of claim 1 , wherein the primers comprise sequences consisting of from 20 to 100 contiguous nucleotides of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID NO:37, SEQ ID NO:39, SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, or SEQ ID NO:53.
4 . The method of claim 1 , wherein the primers comprise sequences consisting of from 20 to 50 contiguous nucleotides of SEQ ID NO:3.
5 . The method of claim 1 , wherein the PCR product is resolved by SSCP, DGGE, ASO or RFLP.
6 . A method for treating glaucoma comprising administering to a patient in need thereof a composition comprising a sequence consisting of at least one compound selected from the group consisting of a BMP2 agonist, a BMP4 agonist, a BMP5 agonist, a BMP7 agonist, a Smad ⅕ agonist, a chordin antagonist, a gremlin antagonist and a follistatin antagonist.
7 . A method for identifying a therapeutic agent for the treatment of glaucoma, said method comprising:
d) obtaining a first composition comprising a population of recombinant cells expressing BMP-2A, BMP4, BMP-5, or BMP7;
e) obtaining a candidate substance;
f) incubating said composition and said candidate substance;
g) testing said composition for its ability to turn on BMP-induced Smad signaling pathways or BMP-regulated gene expression; and
h) identifying a candidate substance that inhibits, or stimulates, BMP-induced Smad signaling pathways or BMP-regulated gene expression.