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bioRxiv · 10.1101/2020.11.03.367151

Involvement of c-Jun N-terminus kinase 2 (JNK2) in Endothelin-1 (ET-1) mediated neurodegeneration of retinal ganglion cells

Kodati, B.·Stankowska, D. L.·Krishnamoorthy, V. R.·Krishnamoorthy, R. R.
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Abstract

PurposeThe goal of this study was to determine if JNK2 plays a causative role in endothelin-mediated loss of RGCs in mice. MethodsJNK2-/- and wild type (C57BL/6) mice were intravitreally injected in one eye with 1 nmole of ET-1, while the contralateral eye was injected with the vehicle. At two time points (2 h and 24 h) following the intravitreal injections, retinal sections were obtained and phosphorylated c-Jun was assessed. 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 7 days post-injection. Retinal flat mounts were stained with antibodies to the RGC marker, Brn3a, and surviving RGCs were quantified. Axonal degeneration was assessed by imaging PPD stained optic nerve sections. ResultsIntravitreal 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, 7 days post injection with ET-1. JNK2-/- mice showed a significant (p=0.36) 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 mice eyes. ConclusionJNK2 appears to play a major role in ET-1 mediated loss of RGCs in mice. Neuroprotective effects of JNK2 following ET-1 administration occur mainly in the soma and not in the axons of RGCs.

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Kodati, B., Stankowska, D. L., Krishnamoorthy, V. R., Krishnamoorthy, R. R.. 2020-11-03. Involvement of c-Jun N-terminus kinase 2 (JNK2) in Endothelin-1 (ET-1) mediated neurodegeneration of retinal ganglion cells. https://doi.org/10.1101/2020.11.03.367151

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