{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:51:35Z","timestamp":1772160695888,"version":"3.50.1"},"reference-count":75,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The axons of retinal ganglion cells (RGCs) form the optic nerve, which relays visual information to the brain. RGC degeneration is the root cause of a variety of blinding diseases linked to optic nerve damage, including glaucoma, the second leading cause of blindness worldwide. The underlying cellular mechanisms of RGC degeneration are largely unclear; yet, they have been connected to excessive production of the signalling molecule nitric oxide (NO) by nitric oxide synthase (NOS). NO activates soluble guanylate cyclase (sGC), which subsequently produces the second messenger cyclic guanosine monophosphate (cGMP). This, in turn, activates protein kinase G (PKG), which can phosphorylate downstream protein targets. To study the role of NO\/cGMP\/PKG signalling in RGC degeneration, we used organotypic retinal explant cultures in which the optic nerve had been severed. We assessed the activity of NOS, RGC death and survival at different times after optic nerve transection. While NOS activity was high right after optic nerve transection, significant RGC loss occurred with a 24\u201348\u2010h delay. We then treated retinal explants with inhibitors selectively targeting either NOS, sGC, PKG, or Kv1.3 and Kv1.6 voltage\u2010gated potassium channels. While all four treatments reduced RGC death, the PKG inhibitor CN238 and the Kv\u2010channel blocker Margatoxin (MrgX) showed the most pronounced rescue effects. Our results confirm an involvement of NO\/cGMP\/PKG signalling in RGC degeneration, highlight the potential of PKG and Kv1\u2010channel targeting drugs for treatment development, and further suggest organotypic retinal explant cultures as a useful model for investigations into optic nerve damage.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70072-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  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