Calcium / Calmodulin–Dependent Protein Kinase in NMDA–Induced Retinal Damage

Abstract

Purpose: : Calcium / calmodulin–dependent protein kinases (CaMKs) are well known as serine / threonine protein kinases and activated by various stresses. In this study, we examined the role of phospholylated calcium / calmodulin–dependent protein kinases II / IV (p–CaMK II / IV) in the rat retina.

Methods: : Two–micro liter of 10 mM (total amount of 20 nmol) NMDA was injected intravitreally into the eyes. We performed immunohistochemistry of p–CaMK II / IV to examine their localization in the retina. Time course of CaMK IV was examined by Western blot analysis 1, 3, 6, 12 and 24 hours after PBS or NMDA injection. KN–93 was used for inhibition of CaMKs and was simultaneously injected with NMDA. We evaluated the cell number of RGCL and the IPL thickness by transverse sections 7 days after the injection.

Results: : p–CaMK II / IV was expressed in the RGCL and the INL 3 hours after the injection. Western blot analysis showed that an increase of CaMK IV appeared from 3 hours after the injection. KN–93 accerelated the cell losses in the RGCL and the thining of the IPL after the injection.

Conclusions: : Activation of CaMKs was involved in stimulation of NMDA receptor and their inhibition accerelated the inner neuronal cell death in retina. Phosphorylation of these CaMKs may cause as endogeneous protective reactions.

Keywords: neuroprotection • ganglion cells • calcium