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Abstract #67566 Published in IGR 17-4
Persistence of intact retinal ganglion cell terminals after axonal transport loss in the DBA/2J mouse model of glaucoma
Smith MA; Xia CZ; Dengler-Crish CM; Fening KM; Inman DM; Schofield BR; Crish SDJournal of Comparative Neurology 2016; 524: 3503-3517
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) using three-dimensional serial block-face scanning electron microscopy (3-D EM) 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 when compared to either transport-intact or control tissue. While 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 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 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. This article is protected by copyright. All rights reserved.
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Classification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)
