Tags

Type your tag names separated by a space and hit enter

Critical pathogenic events underlying progression of neurodegeneration in glaucoma.
Prog Retin Eye Res. 2012 Nov; 31(6):702-19.PR

Abstract

Glaucoma is a common optic neuropathy with a complex etiology often linked to sensitivity to intraocular pressure. Though the precise mechanisms that mediate or transduce this sensitivity are not clear, the axon of the retinal ganglion cell appears to be vulnerable to disease-relevant stressors early in progression. One reason may be because the axon is generally thin for both its unmyelinated and myelinated segment and much longer than the thicker unmyelinated axons of other excitatory retinal neurons. This difference may predispose the axon to metabolic and oxidative injury, especially at distal sites where pre-synaptic terminals form connections in the brain. This idea is consistent with observations of early loss of anterograde transport at central targets and other signs of distal axonopathy that accompany physiological indicators of progression. Outright degeneration of the optic projection ensues after a critical period and, at least in animal models, is highly sensitive to cumulative exposure to elevated pressure in the eye. Stress emanating from the optic nerve head can induce not only distal axonopathy with aspects of dying back neuropathy, but also Wallerian degeneration of the optic nerve and tract and a proximal program involving synaptic and dendritic pruning in the retina. Balance between progressive and acute mechanisms likely varies with the level of stress placed on the unmyelinated axon as it traverses the nerve head, with more acute insult pushing the system toward quicker disassembly. A constellation of signaling factors likely contribute to the transduction of stress to the axon, so that degenerative events along the length of the optic projection progress in retinotopic fashion. This pattern leads to well-defined sectors of functional depletion, even at distal-most sites in the pathway. While ganglion cell somatic drop-out is later in progression, some evidence suggests that synaptic and dendritic pruning in the retina may be a more dynamic process. Structural persistence both in the retina and in central projection sites offers the possibility that intrinsic self-repair pathways counter pathogenic mechanisms to delay as long as possible outright loss of tissue.

Authors+Show Affiliations

Department of Ophthalmology and Visual Sciences, The Vanderbilt Eye Institute, Vanderbilt University School of Medicine, 11435 MRB IV, 2215B Garland Avenue, Nashville, TN 37232, USA. david.j.calkins@vanderbilt.edu

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Review

Language

eng

PubMed ID

22871543

Citation

Calkins, David J.. "Critical Pathogenic Events Underlying Progression of Neurodegeneration in Glaucoma." Progress in Retinal and Eye Research, vol. 31, no. 6, 2012, pp. 702-19.
Calkins DJ. Critical pathogenic events underlying progression of neurodegeneration in glaucoma. Prog Retin Eye Res. 2012;31(6):702-19.
Calkins, D. J. (2012). Critical pathogenic events underlying progression of neurodegeneration in glaucoma. Progress in Retinal and Eye Research, 31(6), 702-19. https://doi.org/10.1016/j.preteyeres.2012.07.001
Calkins DJ. Critical Pathogenic Events Underlying Progression of Neurodegeneration in Glaucoma. Prog Retin Eye Res. 2012;31(6):702-19. PubMed PMID: 22871543.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Critical pathogenic events underlying progression of neurodegeneration in glaucoma. A1 - Calkins,David J, Y1 - 2012/08/01/ PY - 2012/05/27/received PY - 2012/07/16/revised PY - 2012/07/18/accepted PY - 2012/8/9/entrez PY - 2012/8/9/pubmed PY - 2013/3/30/medline SP - 702 EP - 19 JF - Progress in retinal and eye research JO - Prog Retin Eye Res VL - 31 IS - 6 N2 - Glaucoma is a common optic neuropathy with a complex etiology often linked to sensitivity to intraocular pressure. Though the precise mechanisms that mediate or transduce this sensitivity are not clear, the axon of the retinal ganglion cell appears to be vulnerable to disease-relevant stressors early in progression. One reason may be because the axon is generally thin for both its unmyelinated and myelinated segment and much longer than the thicker unmyelinated axons of other excitatory retinal neurons. This difference may predispose the axon to metabolic and oxidative injury, especially at distal sites where pre-synaptic terminals form connections in the brain. This idea is consistent with observations of early loss of anterograde transport at central targets and other signs of distal axonopathy that accompany physiological indicators of progression. Outright degeneration of the optic projection ensues after a critical period and, at least in animal models, is highly sensitive to cumulative exposure to elevated pressure in the eye. Stress emanating from the optic nerve head can induce not only distal axonopathy with aspects of dying back neuropathy, but also Wallerian degeneration of the optic nerve and tract and a proximal program involving synaptic and dendritic pruning in the retina. Balance between progressive and acute mechanisms likely varies with the level of stress placed on the unmyelinated axon as it traverses the nerve head, with more acute insult pushing the system toward quicker disassembly. A constellation of signaling factors likely contribute to the transduction of stress to the axon, so that degenerative events along the length of the optic projection progress in retinotopic fashion. This pattern leads to well-defined sectors of functional depletion, even at distal-most sites in the pathway. While ganglion cell somatic drop-out is later in progression, some evidence suggests that synaptic and dendritic pruning in the retina may be a more dynamic process. Structural persistence both in the retina and in central projection sites offers the possibility that intrinsic self-repair pathways counter pathogenic mechanisms to delay as long as possible outright loss of tissue. SN - 1873-1635 UR - https://www.unboundmedicine.com/medline/citation/22871543/Critical_pathogenic_events_underlying_progression_of_neurodegeneration_in_glaucoma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1350-9462(12)00053-5 DB - PRIME DP - Unbound Medicine ER -