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CaMKIIB Mediates a Survival Response in Retinal Ganglion Cells Subjected to a Glutamate Stimulus

¹From the Departments of Anatomical Sciences and Neurobiology and ²Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, Kentucky.

PURPOSE. During N-methyl-D-aspartate–induced cell death in the neural retina, levels of the nuclear isoform of CaMKII, CaMKIIB, previously reported to be detected only in the midbrain and diencephalon, become elevated. The purpose of this study was to investigate whether CaMKIIB is present specifically in retinal ganglion cells (RGCs) and to determine whether it can be implicated in the cell death or cell survival of signal transduction pathways.

METHODS. Pan-purified RGCs were obtained from the retinas of postnatal day (P)6 to P8 Sprague–Dawley rats. The expression level of CaMKIIB was investigated in RGCs with the aid of RT-PCR and immunostaining under normal and glutamate-stressed conditions. siRNA targeted to CaMKIIB was used to knock down the level of endogenous mRNA in RGCs, and cell viability was tested. The putative role of CaMKIIB in the downstream expression of survival genes such as BDNF was evaluated in CaMKIIB knocked-down RGCs with the aid of RT-PCR, real-time PCR, and immunofluorescence microscopy.

RESULTS. Basal levels of CaMKIIB were expressed in RGCs. Expression levels became increased in response to glutamate treatment and were translocated to the nuclei after a glutamate stimulus. In pan-purified RGCs with knocked down levels of CaMKIIB, a glutamate stimulus led to an increase in cell death. When CaMKIIB was knocked down in RGCs, a corresponding decrease occurred in the level of BDNF expression.

CONCLUSIONS. These data indicate that the presence of basal levels of CaMKIIB in RGCs may afford them some ongoing protection from a stressful environment. In response to the glutamate stimulus, the expression of survival genes such as BDNF may be enhanced through elevation of this particular isoform of the CaMKII gene.

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				A. T. E. Hartwick, C. M. Hamilton, and W. H. Baldridge Glutamatergic calcium dynamics and deregulation of rat retinal ganglion cells J. Physiol., July 15, 2008; 586(14): 3425 - 3446. [Abstract] [Full Text] [PDF]