title: Susceptibility to glaucoma damage related to age and connective tissue mutations in mice.
abstract: The purpose of this research was to study the effects of age and genetic alterations in key connective tissue proteins on susceptibility to experimental glaucoma in mice. We used mice haploinsufficient in the elastin gene (EH) and mice without both alleles of the fibromodulin gene (FM KO) and their wild type (WT) littermates of B6 and CD1 strains, respectively. FM KO mice were tested at two ages: 2 months and 12 months. Intraocular pressure (IOP) was measured by Tonolab tonometer, axial lengths and widths measured by digital caliper post-enucleation, and chronic glaucoma damage was measured using a bead injection model and optic nerve axon counts. IOP in EH mice was not significantly different from WT, but FM KO were slightly lower than their controls (p = 0.04). Loss of retinal ganglion cell (RGC) axons was somewhat, but not significantly greater in young EH and younger or older FM KO strains than in age-matched controls (p = 0.48, 0.34, 0.20, respectively, multivariable regression adjusting for IOP exposure). Older CD1 mice lost significantly more RGC axons than younger CD1 (p = 0.01, multivariable regression). The CD1 mouse strain showed age-dependence of experimental glaucoma damage to RGC in the opposite, and more expected, direction than in B6 mice in which older mice are more resistant to damage. Genetic alteration in two genes that are constituents of sclera, fibromodulin and elastin do not significantly affect RGC loss.
authors.affiliation: Glaucoma Center of Excellence, Wilmer Ophthalmological Institute, Departments of Ophthalmology, Baltimore, MD, United States.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Steinhart
authors.affiliation: Glaucoma Center of Excellence, Wilmer Ophthalmological Institute, Departments of Ophthalmology, Baltimore, MD, United States.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cone-Kimball
authors.affiliation: Glaucoma Center of Excellence, Wilmer Ophthalmological Institute, Departments of Ophthalmology, Baltimore, MD, United States.
authors.forename: Cathy
authors.initials: C
authors.lastname: Nguyen
authors.affiliation: Glaucoma Center of Excellence, Wilmer Ophthalmological Institute, Mechanical Engineering, Johns Hopkins University, Baltimore, MD, United States.
authors.forename: Thao D
authors.initials: TD
authors.lastname: Nguyen
authors.affiliation: Glaucoma Center of Excellence, Wilmer Ophthalmological Institute, Departments of Ophthalmology, Baltimore, MD, United States.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Pease
authors.affiliation: Glaucoma Center of Excellence, Wilmer Ophthalmological Institute, Departments of Ophthalmology, Baltimore, MD, United States.
authors.forename: Shukti
authors.initials: S
authors.lastname: Chakravarti
authors.affiliation: Glaucoma Center of Excellence, Wilmer Ophthalmological Institute, Departments of Ophthalmology, Baltimore, MD, United States.
authors.forename: Ericka N
authors.initials: EN
authors.lastname: Oglesby
authors.affiliation: Glaucoma Center of Excellence, Wilmer Ophthalmological Institute, Departments of Ophthalmology, Baltimore, MD, United States. Electronic address: hquigley@jhmi.edu.
authors.forename: Harry A
authors.initials: HA
authors.lastname: Quigley
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001369:Axons / Q000473:pathology; D001696:Biomechanical Phenomena; D002452:Cell Count; D003238:Connective Tissue / Q000378:metabolism* / Q000473:pathology; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D000071235:Fibromodulin; D020022:Genetic Predisposition to Disease; D005901:Glaucoma / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D007429:Intraocular Pressure; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D012590:Sclera / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; C000604332:Fmod protein, mouse; D011509:Proteoglycans; D000071235:Fibromodulin; D004247:DNA; D004549:Elastin
keywords: biomechanics; elastin; experimental model; fibromodulin; glaucoma; mouse; retinal ganglion cell; sclera