title: 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.
authors.affiliation: Flaum Eye Institute, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Fernandes
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Harder
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Pete A
authors.initials: PA
authors.lastname: Williams
authors.affiliation: Flaum Eye Institute, University of Rochester Medical Center, Rochester, NY, USA; Interdepartmental Graduate Program in Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Rausch
authors.affiliation: Flaum Eye Institute, University of Rochester Medical Center, Rochester, NY, USA; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Kiernan
authors.affiliation: Department of Ophthalmology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: K Saidas
authors.initials: KS
authors.lastname: Nair
authors.affiliation: Department of Molecular Physiology and Biophysics, The University of Iowa, Iowa City, IA, USA; Center for the Prevention and Treatment of Visual Loss, Iowa City Veterans Affairs (VA) Health Care System, Iowa City, IA, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Anderson
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA; The Howard Hughes Medical Institute, Bar Harbor, ME, USA.
authors.forename: Simon W M
authors.initials: SW
authors.lastname: John
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, USA.
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Howell
authors.affiliation: Flaum Eye Institute, University of Rochester Medical Center, Rochester, NY, USA; Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY, USA. Electronic address: richard_libby@urmc.rochester.edu.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Libby
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005901:Glaucoma / Q000235:genetics*; D006801:Humans; D007429:Intraocular Pressure; D051379:Mice; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology
keywords: Axonal degeneration; DBA/2J; Genomics; IOP; Mouse genetics; Neurodegeneration; Neuroinflammation; Trabecular meshwork