Abstract
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 strain and C57BL/6J as a glaucoma-resistant strain were performed to identify genetic loci responsible for the iris disease and high IOP. A recessive locus linked to Tyrp1(b) on chromosome 4 contributes to iris stromal atrophy and high IOP. However, this is not the only important locus. A recessive locus on YBR chromosome 17 causes high IOP independent of the iris stromal atrophy. In specific eyes with high IOP caused by YBR chromosome 17, the drainage angle (through which ocular fluid leaves the eye) is largely open. The YBR alleles of genes on chromosomes 4 and 17 underlie the development of high IOP and glaucoma but do so through independent mechanisms. Together, these two loci act in an additive manner to increase the susceptibility of YBR mice to the development of high IOP. The chromosome 17 locus is important not only because it causes IOP elevation in mice with largely open drainage 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.