Involvement of c-Jun N-terminal kinase 2 (JNK2) in Endothelin-1 (ET-1) Mediated Neurodegeneration of Retinal Ganglion Cells

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dc.creatorKodati, Bindu
dc.creatorStankowska, Dorota L.
dc.creatorKrishnamoorthy, Vignesh R.
dc.creatorKrishnamoorthy, Raghu R.
dc.date.accessioned2022-09-30T17:34:17Z
dc.date.available2022-09-30T17:34:17Z
dc.date.issued2021-05-03
dc.description.abstractPurpose: The goal of this study was to determine whether JNK2 played a causative role in endothelin-mediated loss of RGCs in mice. Methods: JNK2-/- and wild type (C57BL/6) mice were intravitreally injected in one eye with 1 nmole of ET-1, whereas the contralateral eye was injected with the vehicle. At two time points (two hours and 24 hours) after the intravitreal injections, mice were euthanized, and phosphorylated c-Jun was assessed in retinal sections. In a separate set of experiments, JNK2-/- and wild type mice were intravitreally injected with either 1 nmole of ET-1 or its vehicle and euthanized seven days after injection. Retinal flat mounts were stained with antibodies to the RGC marker, Brn3a, and surviving RGCs were quantified. Axonal degeneration was assessed in paraphenylenediamine stained optic nerve sections. Results: Intravitreal ET-1 administration produced a significant increase in immunostaining for phospho c-Jun in wild type mice, which was appreciably lower in the JNK2 -/- mice. A significant (P < 0.05) 26% loss of RGCs was found in wild type mice, seven days after injection with ET-1. JNK2-/- mice showed a significant protection from RGC loss following ET-1 administration, compared to wild type mice injected with ET-1. A significant decrease in axonal counts and an increase in the collapsed axons was found in ET-1 injected wild type mice eyes. Conclusions: JNK2 appears to play a major role in ET-1 mediated loss of RGCs in mice. Neuroprotective effects in JNK2-/- mice following ET-1 administration occur mainly in the soma and not in the axons of RGCs.
dc.description.sponsorshipSupported by NEI (EY028179).
dc.identifier.citationKodati, B., Stankowska, D. L., Krishnamoorthy, V. R., & Krishnamoorthy, R. R. (2021). Involvement of c-Jun N-terminal kinase 2 (JNK2) in Endothelin-1 (ET-1) Mediated Neurodegeneration of Retinal Ganglion Cells. Investigative ophthalmology & visual science, 62(6), 13. https://doi.org/10.1167/iovs.62.6.13
dc.identifier.issn1552-5783
dc.identifier.issue6
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31816
dc.identifier.volume62
dc.publisherARVO Journals
dc.relation.urihttps://doi.org/10.1167/iovs.62.6.13
dc.rights.holderCopyright 2021 The Authors
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceInvestigative Ophthalmology & Visual Science
dc.subject.meshAnimals
dc.subject.meshAxons / pathology
dc.subject.meshBiomarkers / metabolism
dc.subject.meshCell Survival
dc.subject.meshEndothelin-1 / toxicity
dc.subject.meshFemale
dc.subject.meshImmunohistochemistry
dc.subject.meshIntravitreal Injections
dc.subject.meshMale
dc.subject.meshMice
dc.subject.meshMice, Inbred C57BL
dc.subject.meshMice, Knockout
dc.subject.meshMitogen-Activated Protein Kinase 9 / metabolism
dc.subject.meshOptic Nerve / pathology
dc.subject.meshPhosphorylation
dc.subject.meshRetinal Degeneration / chemically induced
dc.subject.meshRetinal Degeneration / enzymology
dc.subject.meshRetinal Ganglion Cells / drug effects
dc.subject.meshRetinal Ganglion Cells / enzymology
dc.subject.meshTranscription Factor Brn-3A / metabolism
dc.titleInvolvement of c-Jun N-terminal kinase 2 (JNK2) in Endothelin-1 (ET-1) Mediated Neurodegeneration of Retinal Ganglion Cells
dc.typeArticle
dc.type.materialtext

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