Retinal neuronal death

Katai N, Yoshimura N. 1999. Apoptotic retinal neuronal death by ischemia-reperfusion is executed by two distinct caspase family proteases. Invest Ophthalmol Vis Sci 40 2697-2705. 

Activation of calpain is usually associated with the progression of a necrotic type of cell death (Wang, 2000). However, neuronal necrosis and apoptosis occur in parallel after ischemic injury in vitro and in vivo (Charriaut-Marlangue et al., 1996). Retinal ischemia causes precocious necrosis of neurons in the ganglion cell layer (GCL) and INL, whereas apoptosis appears as the delayed component of neuronal death associated with transient retinal ischemia (Joo et al., 1999). 

Apoptotic cell death of retinal neurons also contributes to mosaic formation. Rather than obliterating the regularity that the neurons have attained during development, programed cell death actively targets neurons so that a more regular pattern of cell distribution is reached (Jeyarasasingam et al., 1998). 

IL-1 and tumor necrosis factor (TNF) are proinflammatory cytokines. They are produced in response to adverse stimuli. Each cytokine exists as two well-characterized isoforms IL-lot and IL-1P, and TNF-ot and TNF-p, respectively. There is strong evidence for the involvement of IL-1P and TNF ot in the pathogenesis of experimental brain ischemia (Hallenbeck, 2002 Patel et al., 2003). In the retina, transient ischemia causes upregulation of TNF-ot (Fontaine et al., 2002). In the early phase of reperfusion, TNF-ot is primarily upregulated in ganglion cells, amacrine cells, and Muller cells. There is no consensus about the overall efiect of TNF-ot on retinal cell viability. There is an indication that activation of TNF receptor 2 is neuroprotective, whereas activation of TNF receptor 1 augments neuronal death. 

Accelerated apoptotic cell death has been observed in many neurodegenera-tive diseases such as Alzheimer s disease (K7), Huntington disease (W9), amyotrophic lateral sclerosis (K12), cerebellar degeneration (T4), neuron degeneration in Down s syndrome (B16), Parkinson s disease (J1), and retinitis pigmentosa (R1). 

Glutamate is the major excitatory retinal neurotransmitter in retina. It is released by photoreceptors, bipolar cells, and ganglion cells (Sharma and Ehinger, 2003). Normally, the released glutamate remains in the synaptic cleft only for a short time (a few milliseconds). If glutamate levels remain elevated for a prolonged period of time, this can excite neurons to death. This mechanism of cell death is referred to as excitotoxicity. 

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