A variety of inherited animal models with different genetic causes and distinct genetic backgrounds are needed to help dissect the complex genetic etiology of glaucoma. The scarcity of such animal models has hampered progress in glaucoma research. Here, we introduce a new inherited glaucoma model: the inbred mouse strain YBR/EiJ (YBR). YBR mice develop a form of pigmentary glaucoma. They exhibit a progressive age-related pigment dispersing iris disease characterized by iris stromal atrophy. Subsequently, these mice develop elevated intraocular pressure (IOP) and glaucoma. Genetic mapping studies utilizing YBR as a glaucoma susceptible and C57BL/6J as a glaucoma resistant strain was performed to identify genetic loci responsible for the iris disease and high IOP. A recessive locus linked to Tyrp1b on Chr4 contributes to iris stromal atrophy and high IOP. However, this is not the only important locus. A recessive locus on YBR Chr17 causes high IOP independent of the iris stromal atrophy, and in eyes with angles (location of the ocular drainage tissue) that are largely open. The YBR alleles of genes on Chromosomes 4 and 17 underlie the development of high IOP and glaucoma but do so by independent mechanisms. Together, these two loci act in an additive manner to increase the susceptibility of YBR mice to developing high IOP. The Chromosome 17 locus is important not only as it causes IOP elevation in mice with largely open-angles but also because it exacerbates IOP elevation and glaucoma induced by pigment dispersion. Therefore, YBR mice are a valuable resource for studying the genetic etiology of IOP elevation and glaucoma, as well as for testing new treatments.
- Received January 5, 2016.
- Accepted June 3, 2016.
- © 2016. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.