VAV2 and VAV3 as candidate disease genes for spontaneous glaucoma in mice and humans. PLoS One 2010 Feb 04;5(2):e9050
Date
02/09/2010Pubmed ID
20140222Pubmed Central ID
PMC2816215DOI
10.1371/journal.pone.0009050Scopus ID
2-s2.0-77949406694 (requires institutional sign-in at Scopus site) 47 CitationsAbstract
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.
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.
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.
Author List
Fujikawa K, Iwata T, Inoue K, Akahori M, Kadotani H, Fukaya M, Watanabe M, Chang Q, Barnett EM, Swat WAuthor
Edward M. Barnett MD, PhD Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntihypertensive Agents
Eye
Genetic Predisposition to Disease
Glaucoma
Glaucoma, Open-Angle
Humans
Hydrophthalmos
Immunohistochemistry
In Situ Hybridization
Intraocular Pressure
Japan
Mice
Mice, Inbred C57BL
Mice, Knockout
Nerve Degeneration
Optic Disk
Polymorphism, Single Nucleotide
Prostaglandins F, Synthetic
Proto-Oncogene Proteins c-vav
Reverse Transcriptase Polymerase Chain Reaction
