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Expression and activation of mitogen-activated protein kinases in the optic nerve head in a rat model of ocular hypertension.
Mol Cell Neurosci. 2018 04; 88:270-291.MC

Abstract

BACKGROUND

Glaucoma is a leading cause of irreversible blindness manifesting as an age-related, progressive optic neuropathy with associated retinal ganglion cell (RGC) loss. Mitogen-activated protein kinases (MAPKs: p42/44 MAPK, SAPK/JNK, p38 MAPK) are activated in various retinal disease models and likely contribute to the mechanisms of RGC death. Although MAPKs play roles in the development of retinal pathology, their action in the optic nerve head (ONH), where the initial insult to RGC axons likely resides in glaucoma, remains unexplored.

METHODS

An experimental paradigm representing glaucoma was established by induction of chronic ocular hypertension (OHT) via laser-induced coagulation of the trabecular meshwork in Sprague-Dawley rats. MAPKs were subsequently investigated over the following days for expression and activity alterations, using RT-PCR, immunohistochemistry and Western immunoblot.

RESULTS

p42/44 MAPK expression was unaltered after intraocular pressure (IOP) elevation, but there was a significant activation of this enzyme in ONH astrocytes after 6-24 h. Activated SAPK/JNK isoforms were present throughout healthy RGC axons but after IOP elevation or optic nerve crush, they both accumulated at the ONH, likely due to RGC axon transport disruption, and were subject to additional activation. p38 MAPK was expressed by a population of microglia which were significantly more populous following IOP elevation. However it was only significantly activated in microglia after 3 days, and then only in the ONH and optic nerve; in the retina it was solely activated in RGC perikarya.

CONCLUSIONS

In conclusion, each of the MAPKs showed a specific spatio-temporal expression and activation pattern in the retina, ONH and optic nerve as a result of IOP elevation. These findings likely reflect the roles of the individual enzymes, and the cells in which they reside, in the developing pathology following IOP elevation. These data have implications for understanding the mechanisms of ocular pathology in diseases such as glaucoma.

Authors+Show Affiliations

Ophthalmic Research Laboratories, Central Adelaide Local Health Network, Level 7 Adelaide Health & Medical Sciences Building, University of Adelaide, Adelaide, South Australia, Australia; Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: teresa.mammone@sa.gov.au.Ophthalmic Research Laboratories, Central Adelaide Local Health Network, Level 7 Adelaide Health & Medical Sciences Building, University of Adelaide, Adelaide, South Australia, Australia; Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: glyn.chidlow@sa.gov.au.Ophthalmic Research Laboratories, Central Adelaide Local Health Network, Level 7 Adelaide Health & Medical Sciences Building, University of Adelaide, Adelaide, South Australia, Australia; Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: robert.casson@adelaide.edu.au.Ophthalmic Research Laboratories, Central Adelaide Local Health Network, Level 7 Adelaide Health & Medical Sciences Building, University of Adelaide, Adelaide, South Australia, Australia; Department of Ophthalmology and Visual Sciences, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: john.wood2@sa.gov.au.

Pub Type(s)

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

Language

eng

PubMed ID

29408550

Citation

Mammone, Teresa, et al. "Expression and Activation of Mitogen-activated Protein Kinases in the Optic Nerve Head in a Rat Model of Ocular Hypertension." Molecular and Cellular Neurosciences, vol. 88, 2018, pp. 270-291.
Mammone T, Chidlow G, Casson RJ, et al. Expression and activation of mitogen-activated protein kinases in the optic nerve head in a rat model of ocular hypertension. Mol Cell Neurosci. 2018;88:270-291.
Mammone, T., Chidlow, G., Casson, R. J., & Wood, J. P. M. (2018). Expression and activation of mitogen-activated protein kinases in the optic nerve head in a rat model of ocular hypertension. Molecular and Cellular Neurosciences, 88, 270-291. https://doi.org/10.1016/j.mcn.2018.01.002
Mammone T, et al. Expression and Activation of Mitogen-activated Protein Kinases in the Optic Nerve Head in a Rat Model of Ocular Hypertension. Mol Cell Neurosci. 2018;88:270-291. PubMed PMID: 29408550.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Expression and activation of mitogen-activated protein kinases in the optic nerve head in a rat model of ocular hypertension. AU - Mammone,Teresa, AU - Chidlow,Glyn, AU - Casson,Robert J, AU - Wood,John P M, Y1 - 2018/03/20/ PY - 2017/06/01/received PY - 2018/01/03/revised PY - 2018/01/11/accepted PY - 2018/2/7/pubmed PY - 2019/2/1/medline PY - 2018/2/7/entrez KW - Axonal injury KW - Glaucoma KW - Mitogen activated protein kinase (MAPK) KW - Ocular hypertension (OHT) KW - Optic nerve head (ONH) KW - Phosphorylation KW - SAPK/JNK KW - p38 MAPK KW - p42/44 MAPK SP - 270 EP - 291 JF - Molecular and cellular neurosciences JO - Mol Cell Neurosci VL - 88 N2 - BACKGROUND: Glaucoma is a leading cause of irreversible blindness manifesting as an age-related, progressive optic neuropathy with associated retinal ganglion cell (RGC) loss. Mitogen-activated protein kinases (MAPKs: p42/44 MAPK, SAPK/JNK, p38 MAPK) are activated in various retinal disease models and likely contribute to the mechanisms of RGC death. Although MAPKs play roles in the development of retinal pathology, their action in the optic nerve head (ONH), where the initial insult to RGC axons likely resides in glaucoma, remains unexplored. METHODS: An experimental paradigm representing glaucoma was established by induction of chronic ocular hypertension (OHT) via laser-induced coagulation of the trabecular meshwork in Sprague-Dawley rats. MAPKs were subsequently investigated over the following days for expression and activity alterations, using RT-PCR, immunohistochemistry and Western immunoblot. RESULTS: p42/44 MAPK expression was unaltered after intraocular pressure (IOP) elevation, but there was a significant activation of this enzyme in ONH astrocytes after 6-24 h. Activated SAPK/JNK isoforms were present throughout healthy RGC axons but after IOP elevation or optic nerve crush, they both accumulated at the ONH, likely due to RGC axon transport disruption, and were subject to additional activation. p38 MAPK was expressed by a population of microglia which were significantly more populous following IOP elevation. However it was only significantly activated in microglia after 3 days, and then only in the ONH and optic nerve; in the retina it was solely activated in RGC perikarya. CONCLUSIONS: In conclusion, each of the MAPKs showed a specific spatio-temporal expression and activation pattern in the retina, ONH and optic nerve as a result of IOP elevation. These findings likely reflect the roles of the individual enzymes, and the cells in which they reside, in the developing pathology following IOP elevation. These data have implications for understanding the mechanisms of ocular pathology in diseases such as glaucoma. SN - 1095-9327 UR - https://www.unboundmedicine.com/medline/citation/29408550/Expression_and_activation_of_mitogen_activated_protein_kinases_in_the_optic_nerve_head_in_a_rat_model_of_ocular_hypertension_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1044-7431(17)30197-5 DB - PRIME DP - Unbound Medicine ER -