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VAV2 and VAV3 as candidate disease genes for spontaneous glaucoma in mice and humans.
- Source :
-
PloS one [PLoS One] 2010 Feb 04; Vol. 5 (2), pp. e9050. Date of Electronic Publication: 2010 Feb 04. - Publication Year :
- 2010
-
Abstract
- Background: Glaucoma is a leading cause of blindness worldwide. Nonetheless, the mechanism of its pathogenesis has not been well-elucidated, particularly at the molecular level, because of insufficient availability of experimental genetic animal models.<br />Methodology/principal Findings: Here we demonstrate that deficiency of Vav2 and Vav3, guanine nucleotides exchange factors for Rho guanosine triphosphatases, leads to an ocular phenotype similar to human glaucoma. Vav2/Vav3-deficient mice, and to a lesser degree Vav2-deficient mice, show early onset of iridocorneal angle changes and elevated intraocular pressure, with subsequent selective loss of retinal ganglion cells and optic nerve head cupping, which are the hallmarks of glaucoma. The expression of Vav2 and Vav3 tissues was demonstrated in the iridocorneal angle and retina in both mouse and human eyes. In addition, a genome-wide association study screening glaucoma susceptibility loci using single nucleotide polymorphisms analysis identified VAV2 and VAV3 as candidates for associated genes in Japanese open-angle glaucoma patients.<br />Conclusions/significance: Vav2/Vav3-deficient mice should serve not only as a useful murine model of spontaneous glaucoma, but may also provide a valuable tool in understanding of the pathogenesis of glaucoma in humans, particularly the determinants of altered aqueous outflow and subsequent elevated intraocular pressure.
- Subjects :
- Animals
Antihypertensive Agents therapeutic use
Asian People genetics
Eye metabolism
Eye pathology
Glaucoma, Open-Angle ethnology
Glaucoma, Open-Angle genetics
Humans
Hydrophthalmos genetics
Hydrophthalmos metabolism
Immunohistochemistry
In Situ Hybridization
Intraocular Pressure drug effects
Japan
Latanoprost
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Degeneration
Optic Disk metabolism
Optic Disk pathology
Polymorphism, Single Nucleotide
Prostaglandins F, Synthetic therapeutic use
Proto-Oncogene Proteins c-vav deficiency
Proto-Oncogene Proteins c-vav metabolism
Reverse Transcriptase Polymerase Chain Reaction
Genetic Predisposition to Disease
Glaucoma genetics
Proto-Oncogene Proteins c-vav genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 5
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 20140222
- Full Text :
- https://doi.org/10.1371/journal.pone.0009050