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Yanhua Lin, Bryan W. Jones, Kevin Rapp, Marguerite Shaw, Jia-Hui Yang, Carl B. Watt, Robert E. Marc; CaMKII Signaling Is Contributive To Neuritogenesis In Light-Induced Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1846.
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Retinal degenerations (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP), lead to primary loss of photoreceptors and secondary remodeling of the surviving retina. A striking feature of remodeling is neuritogenesis, while the initiators of this process remain unknown. We hypothesize that Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling may influence the evolution of neuritogenesis and subsequent retinal remodeling.
Adult albino mice were exposed to constant intense light (24 h) by excluding one normal night cycle (12 h) to establish the light-induced retinal degeneration (LIRD) animal model. Retinas were harvested at post-light exposure day (pLX) for CaMKII signaling analysis with morphological, metabolic profiling and biochemical parameters.
αCaMKII and βCaMKII were expressed in the neural retina. Low intracellular Ca2+ is known to favor expression of βCaMKII over αCaMKII, and our results showed that light stress immediately increased the protein levels of βCaMKII, but αCaMKII levels showed no change. Increase in βCaMKII/αCaMKII protein ratio correlated with elevated levels of Ca2+-impermeable AMPAR subunit GluR2 and with no change in highly Ca2+-permeable AMPAR subunit GluR1 expression. Inhibitor of CaMKII kinase activity (KN-62) accelerated neuritogenesis while antagonist of AMPAR (NBQX) mitigated neuritogenesis compared with LIRD retina. These changes were followed by bipolar cell neuritogenesis revealed by PKCα staining in the survivor zone.
Even though the gross histology of the neural retina in the survivor zone seems normal early in LIRD, alterations to the fine dendritic circuitry in fact are underway. CaMKII signaling displays large alterations, suggesting potential CaMKII signaling and post-synaptic Ca2+ are responsible for neuritogenesis and reactive neuronal plasticity.
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