Tags

Type your tag names separated by a space and hit enter

Assessment of retinal ganglion cell damage in glaucomatous optic neuropathy: Axon transport, injury and soma loss.
Exp Eye Res. 2015 Dec; 141:111-24.EE

Abstract

Glaucoma is a disease characterized by progressive axonal pathology and death of retinal ganglion cells (RGCs), which causes structural changes in the optic nerve head and irreversible vision loss. Several experimental models of glaucomatous optic neuropathy (GON) have been developed, primarily in non-human primates and, more recently and commonly, in rodents. These models provide important research tools to study the mechanisms underlying glaucomatous damage. Moreover, experimental GON provides the ability to quantify and monitor risk factors leading to RGC loss such as the level of intraocular pressure, axonal health and the RGC population. Using these experimental models we are able to gain a better understanding of GON, which allows for the development of potential neuroprotective strategies. Here we review the advantages and disadvantages of the relevant and most often utilized methods for evaluating axonal degeneration and RGC loss in GON. Axonal pathology in GON includes functional disruption of axonal transport (AT) and structural degeneration. Horseradish peroxidase (HRP), rhodamine-B-isothiocyanate (RITC) and cholera toxin-B (CTB) fluorescent conjugates have proven to be effective reporters of AT. Also, immunohistochemistry (IHC) for endogenous AT-associated proteins is often used as an indicator of AT function. Similarly, structural degeneration of axons in GON can be investigated via changes in the activity and expression of key axonal enzymes and structural proteins. Assessment of axonal degeneration can be measured by direct quantification of axons, qualitative grading, or a combination of both methods. RGC loss is the most frequently quantified variable in studies of experimental GON. Retrograde tracers can be used to quantify RGC populations in rodents via application to the superior colliculus (SC). In addition, in situ IHC for RGC-specific proteins is a common method of RGC quantification used in many studies. Recently, transgenic mouse models that express fluorescent proteins under the Thy-1 promoter have been examined for their potential to provide specific and selective labeling of RGCs for the study of GON. While these methods represent important advances in assessing the structural and functional integrity of RGCs, each has its advantages and disadvantages; together they provide an extensive toolbox for the study of GON.

Authors+Show Affiliations

Retina and Optic Nerve Research Laboratory, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.Retina and Optic Nerve Research Laboratory, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Medical Neuroscience, Dalhousie University, Halifax, Nova Scotia, Canada; Capital District Health Authority, Halifax, Nova Scotia, Canada.Retina and Optic Nerve Research Laboratory, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada.Retina and Optic Nerve Research Laboratory, Dalhousie University, Halifax, Nova Scotia, Canada; Department of Physiology and Biophysics, Dalhousie University, Halifax, Nova Scotia, Canada; Capital District Health Authority, Halifax, Nova Scotia, Canada; Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: bal@dal.ca.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

26070986

Citation

Nuschke, Andrea C., et al. "Assessment of Retinal Ganglion Cell Damage in Glaucomatous Optic Neuropathy: Axon Transport, Injury and Soma Loss." Experimental Eye Research, vol. 141, 2015, pp. 111-24.
Nuschke AC, Farrell SR, Levesque JM, et al. Assessment of retinal ganglion cell damage in glaucomatous optic neuropathy: Axon transport, injury and soma loss. Exp Eye Res. 2015;141:111-24.
Nuschke, A. C., Farrell, S. R., Levesque, J. M., & Chauhan, B. C. (2015). Assessment of retinal ganglion cell damage in glaucomatous optic neuropathy: Axon transport, injury and soma loss. Experimental Eye Research, 141, 111-24. https://doi.org/10.1016/j.exer.2015.06.006
Nuschke AC, et al. Assessment of Retinal Ganglion Cell Damage in Glaucomatous Optic Neuropathy: Axon Transport, Injury and Soma Loss. Exp Eye Res. 2015;141:111-24. PubMed PMID: 26070986.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of retinal ganglion cell damage in glaucomatous optic neuropathy: Axon transport, injury and soma loss. AU - Nuschke,Andrea C, AU - Farrell,Spring R, AU - Levesque,Julie M, AU - Chauhan,Balwantray C, Y1 - 2015/06/09/ PY - 2015/03/03/received PY - 2015/06/01/revised PY - 2015/06/06/accepted PY - 2015/6/14/entrez PY - 2015/6/14/pubmed PY - 2016/2/9/medline KW - Automated quantification KW - Axonal degeneration KW - Fluorescence microscopy KW - Glaucoma KW - Glaucomatous optic neuropathy KW - Immunohistochemistry KW - Quantification methods KW - Retrograde tracer SP - 111 EP - 24 JF - Experimental eye research JO - Exp Eye Res VL - 141 N2 - Glaucoma is a disease characterized by progressive axonal pathology and death of retinal ganglion cells (RGCs), which causes structural changes in the optic nerve head and irreversible vision loss. Several experimental models of glaucomatous optic neuropathy (GON) have been developed, primarily in non-human primates and, more recently and commonly, in rodents. These models provide important research tools to study the mechanisms underlying glaucomatous damage. Moreover, experimental GON provides the ability to quantify and monitor risk factors leading to RGC loss such as the level of intraocular pressure, axonal health and the RGC population. Using these experimental models we are able to gain a better understanding of GON, which allows for the development of potential neuroprotective strategies. Here we review the advantages and disadvantages of the relevant and most often utilized methods for evaluating axonal degeneration and RGC loss in GON. Axonal pathology in GON includes functional disruption of axonal transport (AT) and structural degeneration. Horseradish peroxidase (HRP), rhodamine-B-isothiocyanate (RITC) and cholera toxin-B (CTB) fluorescent conjugates have proven to be effective reporters of AT. Also, immunohistochemistry (IHC) for endogenous AT-associated proteins is often used as an indicator of AT function. Similarly, structural degeneration of axons in GON can be investigated via changes in the activity and expression of key axonal enzymes and structural proteins. Assessment of axonal degeneration can be measured by direct quantification of axons, qualitative grading, or a combination of both methods. RGC loss is the most frequently quantified variable in studies of experimental GON. Retrograde tracers can be used to quantify RGC populations in rodents via application to the superior colliculus (SC). In addition, in situ IHC for RGC-specific proteins is a common method of RGC quantification used in many studies. Recently, transgenic mouse models that express fluorescent proteins under the Thy-1 promoter have been examined for their potential to provide specific and selective labeling of RGCs for the study of GON. While these methods represent important advances in assessing the structural and functional integrity of RGCs, each has its advantages and disadvantages; together they provide an extensive toolbox for the study of GON. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/26070986/Assessment_of_retinal_ganglion_cell_damage_in_glaucomatous_optic_neuropathy:_Axon_transport_injury_and_soma_loss_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(15)00193-1 DB - PRIME DP - Unbound Medicine ER -