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Retinal ganglion cells downregulate gene expression and lose their axons within the optic nerve head in a mouse glaucoma model.

Abstract
Little is known about molecular changes occurring within retinal ganglion cells (RGCs) before their death in glaucoma. Taking advantage of the fact that gamma-synuclein (Sncg) mRNA is expressed specifically and highly in adult mouse RGCs, we show in the DBA/2J mouse model of glaucoma that there is not only a loss of cells expressing this gene, but also a downregulation of gene expression of Sncg and many other genes within large numbers of RGCs. This downregulation of gene expression within RGCs occurs together with reductions in FluoroGold (FG) retrograde transport. Surprisingly, there are also large numbers of Sncg-expressing cells without any FG labeling, and among these many that have a marker previously associated with disconnected RGCs, accumulation of phosphorylated neurofilaments in their somas. These same diseased retinas also have large numbers of RGCs that maintain the intraocular portion while losing the optic nerve portion of their axons, and these disconnected axons terminate within the optic nerve head. Our data support the view that RGC degeneration in glaucoma has two separable stages: the first involves atrophy of RGCs, whereas the second involves an insult to axons, which causes the degeneration of axon portions distal to the optic nerve head but does not cause the immediate degeneration of intraretinal portions of axons or the immediate death of RGCs.
AuthorsIleana Soto, Ericka Oglesby, Brian P Buckingham, Janice L Son, Elisha D O Roberson, Michael R Steele, Denise M Inman, Monica L Vetter, Philip J Horner, Nicholas Marsh-Armstrong
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 28 Issue 2 Pg. 548-61 (Jan 09 2008) ISSN: 1529-2401 [Electronic] United States
PMID18184797 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Stilbamidines
  • gamma-Synuclein
Topics
  • Age Factors
  • Animals
  • Axons (pathology)
  • Axotomy (methods)
  • Disease Models, Animal
  • Down-Regulation (physiology)
  • Glaucoma (complications, pathology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Nerve Degeneration (etiology, physiopathology)
  • Nerve Tissue Proteins (genetics, metabolism)
  • Optic Disk (pathology, physiopathology)
  • RNA, Messenger (metabolism)
  • Retinal Ganglion Cells (physiology)
  • Species Specificity
  • Stilbamidines (metabolism)
  • gamma-Synuclein (genetics, metabolism)

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