title: Intrinsic axonal degeneration pathways are critical for glaucomatous damage.
abstract: Glaucoma is a neurodegenerative disease affecting 70million people worldwide. For some time, analysis of human glaucoma and animal models suggested that RGC axonal injury in the optic nerve head (where RGC axons exit the eye) is an important early event in glaucomatous neurodegeneration. During the last decade advances in molecular biology and genome manipulation have allowed this hypothesis to be tested more critically, at least in animal models. Data indicate that RGC axon degeneration precedes soma death. Preventing soma death using mouse models that are mutant for BAX, a proapoptotic gene, is not sufficient to prevent the degeneration of RGC axons. This indicates that different degeneration processes occur in different compartments of the RGC during glaucoma. Furthermore, the Wallerian degeneration slow allele (Wld(s)) slows or prevents RGC axon degeneration in rodent models of glaucoma. These experiments and many others, now strongly support the hypothesis that axon degeneration is a critical pathological event in glaucomatous neurodegeneration. However, the events that lead from a glaucomatous insult (e.g. elevated intraocular pressure) to axon damage in glaucoma are not well defined. For developing new therapies, it will be necessary to clearly define and order the molecular events that lead from glaucomatous insults to axon degeneration.
authors.affiliation: The Howard Hughes Medical Institute, The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. gareth.howell@jax.org
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Howell
authors.forename: Ileana
authors.initials: I
authors.lastname: Soto
authors.forename: Richard T
authors.initials: RT
authors.lastname: Libby
authors.forename: Simon W M
authors.initials: SW
authors.lastname: John
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology*; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D012165:Retinal Ganglion Cells / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D014855:Wallerian Degeneration / Q000378:metabolism / Q000473:pathology