Diagnostic method for glaucoma

• US 20050069893A1
• Filed: 03/01/2002
• Published: 03/31/2005
• Est. Priority Date: 03/01/2002
• Status: Abandoned Application

• Current Assignee: Josef Flammer, Olga Golubnitschaja
• Original Assignee: Josef Flammer, Olga Golubnitschaja
• Inventors: Flammer, Josef, Golubnitschaja, Olga
• Application Number:
  US10/506,138
• Publication Number:
  US 20050069893A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/158 Expression markers

Abstract

The present invention relates to an ex vivo method for the diagnosis and/or prediction of glaucoma. Said method comprises detecting in a tissue and/or blood sample of a human individual an altered gene expression pattern of at least genes selected from the group of genes related to tissue remodeling. Furthermore, the invention relates to a DNA microarray comprising nucleic acid probes of genes of the specified gene group.

Claims

1. An ex vivo method for the diagnosis and/or prediction of glaucoma comprising

detecting in a tissue and/or blood sample of a human individual an altered gene expression pattern of genes selected from at least a group of genes related to tissue remodeling.

2. The method according to claim 1, wherein said gene expression pattern further comprises genes selected from a group of genes related to DNA repair and/or a group of genes related to cell adhesion and/or a group of genes related to ischemia/reperfusion injury or genes in consequence of the glaucomatous damage.

3. The method according to claim 2, wherein said gene expression pattern comprises a total of at least 4 genes, at least one from each of the four gene groups.

4. The method according to claim 1, wherein said altered gene expression pattern is determined at a transcriptional level.

5. The method according to claim 1, wherein the group of genes related to tissue remodeling comprises the following genes:

metalloproteinases, metalloproteinase inhibitors and proteinase 3.

6. The method according to claim 2, wherein the group of genes related to DNA-repair comprises the following genes:

XPGC, 14-3-3 σ

, p53, MDR-X, survivin, DEAD box X isoform protein (DBX), X-linked retinopathy protein, STM2 gene familial Alzheimer'"'"'s disease, MRCK (myotonic dystrophy kinase-related cdc42 binding kinase), thioredoxin, NFkappB, inhibitor of apoptosis protein 1 (HIAP1, API1), IAP homolog C, TNFR2-TRAF signaling complex protein, MIHC, cyclin A1, guanine nucleotide-binding-protein G(I)/G(S)/G(T)beta subunit 1 (GNB1), transducin beta-1 subunit.

7. The method according to claim 2, wherein the group of genes related to cell adhesion comprises the following genes:

E-cadherin, cytochrome P450, cyclooxygenase-2, rho GDP dissociation inhibitor 1, rho GDI alpha, ARHGDIA, thymosin beta, VEGEFR 1, tyrosine protein kinase receptor SFLT, phospholipase C gamma 1,1-phosphatidyl-inositol-4,5-bisphosphate-phosphodiesterase gamma 1, PLC-II, PLC-148, 68 kDa type I phosphatidyl-inositol-4-phosphate-5-kinase alpha kinase, 1-phosphatidylinositol-4-phosphate kinase, diphospho-inositide kinase, G protein-activated inward rectifier potassium channel 3, KIR 3.3, guanine nucleotide-binding protein G(I)/G(S)/G(T) beta-subunit 1, transducin beta-1 subunit, Rac alpha serine/threonine kinase, protein kinase B, c-akt, akt 1.

8. The method according to claim 2, wherein the group of genes related to ischemia/reperfusion injury or in consequence of glaucomatous damage comprises the following genes:

20S proteosome, NTP, Jun-D, c-jun N-terminal kinase (JNKK), JNK activating kinase 1 (JNKK1), MAP kinase 4 (MKK4), SRp20 splicing factor, lymphocyte-IgE-receptor, thromboxan A2 receptor, Na+/K+-ATPase, ITK, alkaline phosphatase.

9. The method according to claim 1, wherein said altered gene expression Pattern is determined in white blood cells.

17. The method of claim 3, wherein said gene expression pattern comprises a total of at least 8 genes.

18. The method of claim 6, wherein said white blood cells are peripheral lymphocytes, monocytes or stem cells.

10. An array of nucleic acid probes immobilized on a solid support, wherein said array comprises at least nucleic acid probes of genes selected from a group of genes related to tissue remodeling.

11. The array according to claim 10, wherein said array further comprises nucleic acid probes of genes selected from a group of genes related to DNA repair and/or a group of genes related cell adhesion and/or a group of genes related to ischemia/reperfusion injury or genes in consequence of the glaucomatous damage.

12. The array according to claim 11, wherein the nucleic acid probes are selected from genes for

metalloproteinases, metalloproteinase inhibitors and proteinase 3,

XPGC, 14-3-3 σ

, p53, MDR-X, survivin, DEAD box X isoform protein (DBX), X-linked retinopathy protein, STM2 gene familial Alzheimer'"'"'s disease, MRCK (myotonic dystrophy kinase-related cdc42 binding kinase), thioredoxin, NFkappB, inhibitor of apoptosis protein 1 (HIAP1, API1), IAP homolog C, TNFR2-TRAF signaling complex protein, MIHC, cyclin A1, guanine nucleotide-binding-protein G(I)/G(S)/G(T)beta subunit 1 (GNB1), transducin beta-1 subunit,

E-cadherin, cytochrome P450, cyclooxygenase-2, rho GDP dissociation inhibitor 1, rho GDI alpha, ARHGDIA, thymosin beta, VEGEFR 1, tyrosine protein kinase receptor SFLT, phospholipase C gamma 1,1-phosphatidyl-inositol-4,5-bisphosphate-phosphodiesterase gamma 1, PLC-II, PLC-148, 68 kDa type I phosphatidyl-inositol-4-phosphate-5-kinase alpha kinase, 1-phosphatidylinositol-4-phosphate kinase, diphospho-inositide kinase, G protein-activated inward rectifier potassium channel 3, KIR 3.3, guanine nucleotide-binding protein G(I)/G(S)/G(T) beta-subunit 1, transducin beta-1 subunit, Rac alpha serine/threonine kinase, protein kinase B, c-akt, akt 1, and

20S proteosome, NTP, Jun-D, c-jun N-terminal kinase (JNKK), JNK activating kinase 1 (JNKK1), MAP kinase 4 (MKK4), SRp20 splicing factor, lymphocyte-IgE-receptor, thromboxan A2 receptor, Na+/K+-ATPase, ITK or alkaline phosphatase.

13. The array according claim 11, wherein said array consists essentially of nucleic acid probes of genes of said gene groups.

19. An ex vivo method for the diagnosis and/or prediction of glaucoma comprising:

providing the array of claim 10, and

detecting in a tissue and/or blood sample of a human individual an altered gene expression pattern.

20. An ex vivo method for the diagnosis and/or prediction of glaucoma comprising:

providing the array of claim 11, and

detecting in a tissue and/or blood sample of a human individual an altered gene expression pattern.

21. An ex vivo method for the diagnosis and/or prediction of glaucoma comprising:

providing the array of claim 12, and

detecting in a tissue and/or blood sample of a human individual an altered gene expression pattern.

14. (Cancelled)

15. (Cancelled)

16. (Cancelled)

22. A method for treating a patient diagnosed with glaucoma comprising:

administering to said patient an effective amount of at least one gene of the following groups of genes;

(1) genes related to tissue remodeling,

(2) genes related to DNA repair,

(3) genes related to cell adhesion,

(4) genes related to ischemia/reperfusion injury or genes expressed in consequence of the glaucomatous damage, or

combinations thereof,

wherein said method is somatic gene therapy.

23. The method of claim 22, wherein

the group of genes in (1) comprises metalloproteinases, metalloproteinase inhibitors and proteinase 3,

the group of genes in (2) comprises XPGC, 14-3-3 σ

, p53, MDR-X, survivin, DEAD box X isoform protein (DBX), X-linked retinopathy protein, STM2 gene familial Alzheimer'"'"'s disease, MRCK (myotonic dystrophy kinase-related cdc42 binding kinase), thioredoxin, NFkappB, inhibitor of apoptosis protein 1 (HIAP1, API1), IAP homolog C, TNFR2-TRAF signaling complex protein, MIHC, cyclin A1, guanine nucleotide-binding-protein G(I)/G(S)/G(T)beta subunit 1 (GNB1) and transducin beta-1 subunit,

the group of genes in (3) comprises E-cadherin, cytochrome P450, cyclooxygenase-2, rho GDP dissociation inhibitor 1, rho GDI alpha, ARHGDIA, thymosin beta, VEGEFR 1, tyrosine protein kinase receptor SFLT, phospholipase C gamma 1,1-phosphatidyl-inositol-4,5-bisphosphate-phosphodiesterase gamma 1, PLC-II, PLC-148, 68 kDa type I phosphatidyl-inositol-4-phosphate-5-kinase alpha kinase, 1-phosphatidylinositol-4-phosphate kinase, diphospho-inositide kinase, G protein-activated inward rectifier potassium channel 3, KIR 3.3, guanine nucleotide-binding protein G(I)/G(S)/G(T) beta-subunit 1, transducin beta-1 subunit, Rac alpha serine/threonine kinase, protein kinase B and c-akt, akt 1; and

the group of genes in (4) comprises 20S proteosome, NTP, Jun-D, c-jun N-terminal kinase (JNKK), JNK activating kinase 1 (JNKK1), MAP kinase 4 (MKK4), SRp20 splicing factor, lymphocyte-IgE-receptor, thromboxan A2 receptor, Na+/K+-ATPase, ITK or alkaline phosphatase.