Role Of Extracellular Signal-regulated Kinase In Glutamate-stimulated Apoptosis Of Rat Retinal Ganglion Cells

Recent researches have suggested that glutamate is a final common pathway for neurologic disorders. The link between glutamate and apotosis of retinal ganglion cells (RGC) of glaucoma has been widely studied and confirmed. Neuroprotection is a potential treatment for glaucomatous optic neuropathy which may independently lower intraocular pressure (IOP). It has been supported by laboratory studies or some clinical studies that interruption of each stage of this schema is neuroprotective. It may therefore be possible to get a breakthrough in the treatment of glaucoma by blocking the pathways of glutamate. However, some side effects which are caused by blocking its normal functions puzzled clinical practice. With the rising of researches on the role of extracelluar signal-regulated protein kinase (ERK) in central nervous system (CNS), researchers confirmed that expression of phosphorylatd ERK enhanced in rat retina of chronic IOP animal experimental models and galucomaous patients with normal IOP. ERK is one of the important members in the family of Mitogen activated protein kinases (MAPKs), which can give different responses to stimulus such as mitomycin, hormone, excitotoxin, etc.Activation of the ERK pathway results in the modulation of transcriptional activity leading to cell growth, adaption, differentiation and apoptosis. Previous studies suggest that estrogen prevents rat cerebral cortex neuron apoptosis by activation of ERK signal pathway. However, the role of ERK in RGC death induced by glutamate is still unknown. Therefore, it is worth to further investigate whether it functions as proapoptotic or antiapoptotic. In this study, we determine the role of the activated ERK in rat retina after intravitreal injections of glutamate.The experiment was composed of two parts, the first part was to build animal experimental model of glutamate exitotoxicity injury rat retina and to observe the expression of ERK in retina. In experimental group, one eye received an intravitreal glutamate injection, while the contralateral eye was injected saline as control. All rats' eyes were enculaeated 3 or 7 days after injections, the expression of activated ERK was observed by immunohistochemistry of retinal cryosections. There was little expression of phosphorylated ERK in the ganglion cell layer (GCL) of the normal retina. ERK phosphorylation was evident in the inner nuclear layer (INL), inner plexiform layer (IPL), and GCL at 3 days after glutamate injection. However, the immunoreactivity of ERK increased remarkably, not only in the INL, but also in the fibers. Seven days after glutamate injection, very intense p-ERK immuoreactivity was observed in the radial processes extending vertically through the whole retina. By image analysis, we found that there was no statistically difference between experimental group and control group after 3 days injections, and there was significant difference between two groups after 7 days injection. These results showed that exogenous glutamate had a toxicity injury on rat retina after 7 days intravitreal glutamate injections, and...