title: Persistence of intact retinal ganglion cell terminals after axonal transport loss in the DBA/2J mouse model of glaucoma.
abstract: Axonal transport defects are an early pathology occurring within the retinofugal projection of the DBA/2J mouse model of glaucoma. Retinal ganglion cell (RGC) axons and terminals are detectable after transport is affected, yet little is known about the condition of these structures. We examined the ultrastructure of the glaucomatous superior colliculus (SC) with three-dimensional serial block-face scanning electron microscopy to determine the distribution and morphology of retinal terminals in aged mice exhibiting varying levels of axonal transport integrity. After initial axonal transport failure, retinal terminal densities did not vary compared with either transport-intact or control tissue. Although retinal terminals lacked overt signs of neurodegeneration, transport-intact areas of glaucomatous SC exhibited larger retinal terminals and associated mitochondria. This likely indicates increased oxidative capacity and may be a compensatory response to the stressors that this projection is experiencing. Areas devoid of transported tracer label showed reduced mitochondrial volumes as well as decreased active zone number and surface area, suggesting that oxidative capacity and synapse strength are reduced as disease progresses but before degeneration of the synapse. Mitochondrial volume was a strong predictor of bouton size independent of pathology. These findings indicate that RGC axons retain connectivity after losing function early in the disease process, creating an important therapeutic opportunity for protection or restoration of vision in glaucoma. J. Comp. Neurol. 524:3503-3517, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, 44272.|Integrated Pharmaceutical Medicine Program, Northeast Ohio Medical University, Rootstown, Ohio, 44272.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Smith
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, 44272.
authors.forename: Christina Z
authors.initials: CZ
authors.lastname: Xia
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, 44272.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Dengler-Crish
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, 44272.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Fening
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, 44272.
authors.forename: Denise M
authors.initials: DM
authors.lastname: Inman
authors.affiliation: Department of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, Ohio, 44272.
authors.forename: Brett R
authors.initials: BR
authors.lastname: Schofield
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, 44272. scrish@neomed.edu.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Crish
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology; D004195:Disease Models, Animal; D005901:Glaucoma / Q000378:metabolism / Q000473:pathology*; D021621:Imaging, Three-Dimensional; D008811:Mice, Inbred DBA; D008855:Microscopy, Electron, Scanning; D008928:Mitochondria / Q000473:pathology; D056347:Neuroanatomical Tract-Tracing Techniques; D012044:Regression Analysis; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology*; D013477:Superior Colliculi / Q000378:metabolism / Q000473:pathology*; D013569:Synapses / Q000378:metabolism / Q000473:pathology*; D014795:Visual Pathways / Q000378:metabolism / Q000473:pathology
keywords: RRID:IMSR_JAX:000671; RRID:IMSR_JAX:007048; RRID:SCR_002716; RRID:SCR_002865; bouton; mitochondria; neurodegeneration; retinal; superior colliculus; synapse