Using genetic mouse models to gain insight into glaucoma: Past results and future possibilities

Abstract

While all forms of glaucoma are characterized by a specific pattern of retinal ganglion cell death, they are clinically divided into several distinct subclasses, including normal tension glaucoma, primary open angle glaucoma, congenital glaucoma, and secondary glaucoma. For each type of glaucoma there are likely numerous molecular pathways that control susceptibility to the disease. Given this complexity, a single animal model will never precisely model all aspects of all the different types of human glaucoma. Therefore, multiple animal models have been utilized to study glaucoma but more are needed. Because of the powerful genetic tools available to use in the laboratory mouse, it has proven to be a highly useful mammalian system for studying the pathophysiology of human disease. The similarity between human and mouse eyes coupled with the ability to use a combination of advanced cell biological and genetic tools in mice have led to a large increase in the number of studies using mice to model specific glaucoma phenotypes. Over the last decade, numerous new mouse models and genetic tools have emerged, providing important insight into the cell biology and genetics of glaucoma. In this review, we describe available mouse genetic models that can be used to study glaucoma-relevant disease/pathobiology. Furthermore, we discuss how these models have been used to gain insights into ocular hypertension (a major risk factor for glaucoma) and glaucomatous retinal ganglion cell death. Finally, the potential for developing new mouse models and using advanced genetic tools and resources for studying glaucoma are discussed.

Comprehensive analysis of mouse retinal mononuclear phagocytes

“…This protocol described here is now routinely established in the authors´ laboratories and can be principally applied to any project related to retinal disease that involves mononuclear phagocyte reactivity. Such models of ocular disease include all genetic mouse lines for retinal dystrophies and experimental models for uveitis, glaucoma, diabetic retinopathy, retinopathy of prematurity, AMD, and many others [42][43][44][45][46][47][48] .…”

Integrative properties of retinal ganglion cell electrical responsiveness depend on neurotrophic support and genotype in the mouse

“…DBA/2J mice (D2) develop a pigment-dispersing iris disease caused by mutations in two genes, Gpnmb and Tyrp1, which leads to age-related IOP elevation and RGC loss (Howell et al, 2007a; Libby et al, 2005). D2 mice are the most used genetic model of glaucoma (Fernandes et al, 2015). However, a congenic strain of B6 mice that has the same Tyrp1 and Gpnmb mutations as DBA/2J mice and develops the same degree of iris disease, is resistant to IOP elevation and does not develop glaucoma (Anderson et al, 2006; Howell et al, 2007a).…”

Expansions of the neurovascular scleral canal and contained optic nerve occur early in the hypertonic saline rat experimental glaucoma model

“…While the nonhuman primate experimental glaucoma model (Burgoyne, 2015b) benefits from optic nerve head (ONH) anatomy and physiology that is similar to the human ONH, the model is impractical for studies that require large sample sizes. By contrast, rodent models (Crowston et al, 2015; Fernandes et al, 2015; Morgan and Tribble, 2015; Morrison et al, 2015; Overby and Clark, 2015; Pang et al, 2015) display pathophysiologic changes that are comparable to human glaucoma, despite substantial differences in ONH anatomy.…”