Involvement of the c-Jun N-terminus kinase (JNK) pathway in Endothelin (ET-1) mediated neurodegeneration of retinal ganglion cells

dc.creatorKodati, Bindu
dc.creatorStankowska, Dorota
dc.creatorKrishnamoorthy, Vignesh
dc.creatorKrishnamoorthy, Raghu
dc.date.accessioned2021-04-30T15:01:54Z
dc.date.available2021-04-30T15:01:54Z
dc.date.issued2021
dc.description.abstractPURPOSE: Endothelins contribute to neurodegeneration in glaucoma, however, the mechanisms are not completely understood. The goal of this study was to determine if JNK2 plays a causative role in endothelin-1 (ET-1)-mediated loss of RGCs in mice. METHODS: JNK2-/- and wild type (C57BL6) mice (n=4) were intravitreally injected in one eye with 2 nmoles of ET-1, while the contralateral eye was injected with 2 µl of vehicle. The mice were euthanized at 2 h and 24 h post-injection. Retinal sections from the JNK2-/- and wild type (C57BL6) mice were used for immunohistochemical analysis of the phosphorylation of JNK substrate, c-Jun. In a separate set of experiments, JNK2 -/- and wild type mice (n=6) were intravitreally injected with either 2 nmoles of ET-1 or vehicle, and euthanized 7 days post-injection. RGC counts and axonal degeneration were assessed. 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. Following ET-1 administration, a significant (p< 0.05) 26% loss of RGCs was found in wild type mice, while JNK2-/- mice showed no significant (p=0.36) loss of RGCs. A significant decrease in the axonal counts and an increase in the collapsed axons was found in ET-1 injected eyes in wild type mice. CONCLUSION: JNK2 appears to play a major role in ET-1 mediated loss of RGCs in mice.
dc.description.sponsorshipNIH Grant EY028179
dc.identifier.urihttps://hdl.handle.net/20.500.12503/30531
dc.language.isoen
dc.titleInvolvement of the c-Jun N-terminus kinase (JNK) pathway in Endothelin (ET-1) mediated neurodegeneration of retinal ganglion cells
dc.typeposter
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