Genetic modification of glaucoma associated phenotypes between AKXD-28/Ty and DBA/2J mice

AKXD-28/Ty mice develop glaucoma characterized by intraocular pressure elevation, retinal ganglion loss, and optic nerve excavation. In AKXD-28/Ty, isa causes an iris stromal atrophy phenotype as in DBA/2J. However, the iris pigment dispersion phenotype associated with ipd in DBA/2J does not occur in AKXD-28/Ty. Additionally, a greater severity and speed of retinal and optic nerve damage following intraocular pressure elevation in AKXD-28/Ty compared to DBA/2J mice suggests that AKXD-28/Ty is more susceptible to pressure-induced cell death.The consequences of the ipd and isa mutations are modified in the AKXD-28/Ty background. These strains provide a resource for the identification of modifier genes that modulate pigment dispersion and susceptibility to pressure-induced cell death.Glaucoma is a prevalent group of retinal and optic nerve neuropathies that currently renders approximately 67 million people worldwide at risk for developing significant vision loss, including blindness [1]. Glaucoma involves the death of retinal ganglion cells (RGCs) and their axons, and is characterized by atrophic excavation of the optic nerve [2,3,4]. Glaucoma is usually associated with high intraocular pressure (IOP) resulting from an increased resistance to drainage of aqueous humor. Not all people with high IOP develop glaucoma [5], however, suggesting that other factors, such as genetic susceptibility to pressure-induced damage, interact with IOP to cause damage. The occurrence of glaucomatous damage in individuals without high IOP and the benefit of lowering IOP in some of these individuals further suggest multiple factors determine an individual's susceptibility to pressure-induced damage [6]. The nature of the factors participating in glaucomatous events, particularly those influencing disease progression and modifying disease severity in different individuals, remain largely unknown. Increased understanding of factors contributing to glaucoma will suggest new therapeutic strate