title: Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma.
abstract: Here, we use a mouse model (DBA/2J) to readdress the location of insult(s) to retinal ganglion cells (RGCs) in glaucoma. We localize an early sign of axon damage to an astrocyte-rich region of the optic nerve just posterior to the retina, analogous to the lamina cribrosa. In this region, a network of astrocytes associates intimately with RGC axons. Using BAX-deficient DBA/2J mice, which retain all of their RGCs, we provide experimental evidence for an insult within or very close to the lamina in the optic nerve. We show that proximal axon segments attached to their cell bodies survive to the proximity of the lamina. In contrast, axon segments in the lamina and behind the eye degenerate. Finally, the Wld(s) allele, which is known to protect against insults to axons, strongly protects against DBA/2J glaucoma and preserves RGC activity as measured by pattern electroretinography. These experiments provide strong evidence for a local insult to axons in the optic nerve.
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA.
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Howell
authors.forename: Richard T
authors.initials: RT
authors.lastname: Libby
authors.forename: Tatjana C
authors.initials: TC
authors.lastname: Jakobs
authors.forename: Richard S
authors.initials: RS
authors.lastname: Smith
authors.forename: F Campbell
authors.initials: FC
authors.lastname: Phalan
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Barter
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Barbay
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Marchant
authors.forename: Nagaraju
authors.initials: N
authors.lastname: Mahesh
authors.forename: Vittorio
authors.initials: V
authors.lastname: Porciatti
authors.forename: Alan V
authors.initials: AV
authors.lastname: Whitmore
authors.forename: Richard H
authors.initials: RH
authors.lastname: Masland
authors.forename: Simon W M
authors.initials: SW
authors.lastname: John
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D019610:Cytoprotection / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D004596:Electroretinography; D005260:Female; D005901:Glaucoma / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009901:Optic Nerve Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000473:pathology*; D013997:Time Factors; D014855:Wallerian Degeneration / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494827:Bax protein, mouse; D051028:bcl-2-Associated X Protein