VAV2 and VAV3 as Candidate Disease Genes for Spontaneous Glaucoma in Mice and Humans

Fujikawa Keiko; Iwata Takeshi; Inoue Kaoru; Akahori Masakazu; Kadotani Hanako; Fukaya Masahiro; Watanabe Masahiko; Chang Qing; Barnett Edward M.; Swat Wojciech

Title	en VAV2 and VAV3 as Candidate Disease Genes for Spontaneous Glaucoma in Mice and Humans
Creator	en Fujikawa, Keiko en Iwata, Takeshi en Inoue, Kaoru NRID 1000080133718 en Akahori, Masakazu en Kadotani, Hanako en Fukaya, Masahiro NRID 1000010360900 en Watanabe, Masahiko NRID 1000070210945 en Chang, Qing en Barnett, Edward M. en Swat, Wojciech
Accessrights	open access
Rights	http://creativecommons.org/licenses/by/2.5/ en Creative Commons Attribution
Subject	NDC 496
Description	Abstract en 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.
Publisher	en Public Library of Science
Date	Issued2010-02-04
Language	eng
Resource Type	journal article
Version Type	VoR
Identifier	HDL http://hdl.handle.net/2115/42691
Relation	isIdenticalTo DOI https://doi.org/10.1371/journal.pone.0009050
Journal	EISSN 1932-6203 en PLoS ONE Volume Number5 Issue Number2 Page Starte9050
File	fulltext inoue_pone.pdf 737.89 KB (application/pdf) Issued2010-02-04
Oaidate	2023-07-26