Retinal excitotoxicity

IDENTIFICATION OF NOVEL PHARMACOLOGICAL TARGETS TO MINIMIZE EXCITOTOXIC RETINAL DAMAGE... 

III. Blockade of Excitotoxicity Sustains the PI3-K/Akt Prosurvival Pathway in Retinal Ischemia... 

Hare, W. A., and Wheeler, L. (2009). Experimental glutamatergic excitotoxicity in rabbit retinal ganglion cells Block by memantine. Invest. Ophthalmol. Vis. Sci. First published on January 10, 2009 as doi 10.1167 /iovs.08-2103-... 

Complementary to vascular compromise and mechanically impaired axoplasmic flow, additional pathogenic mechanisms (Figures 30.3 30.4) that underlie glaucomatous optic neuropathy include excitotoxic damage from excessive retinal glutamate, peroxynitrite toxicity from increased nitric oxide synthase activity, immune-media ted nerve damage, and oxidative stress (Naskar and Dreyer, 2001). 

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. 

Excitotoxicity has been imphcated in a number of retinal disorders, especially the ones in which ischemia plays a key role. These conditions include glaucoma and diabetic retinopathy. The role of excitotoxicity in glaucoma has been controversial, but in animal models excitotoxicity has been shown to cause ganghon cell damage. 

Fleidinger V, Dreyfus H, Sahel J, Christen Y, Hicks D. 1998. Excitotoxic damage of retinal glial cells depends upon normal neuron-glial interactions. Glia 23 146-155. 

Joo CK, Choi JS, Ko HW, Park KY, Sohn S, et al. 1999. Necrosis and apoptosis after retinal ischemia Involvement of NMDA-mediated excitotoxicity and p53. Invest Ophthalmol Vis Sci 40 713-720. 

Wehrwein, E. Xhompson, S. A. Coulibaly, S. F. Linn, D. M. Linn, C. L. Acetylcholine protection of adult pig retinal ganglion cells from glutamate-induced excitotoxicity. Investigative Ophthalmol. Visual Sci. 2004, 45, 1531-1543. 

Matteucci, A. Frank, C. Domenici, M. R. Balduzzi, M. Paradisi, S. Camovale-Scalzo, G. Scorcia, G. Malchiodi-Albedi, F. Curcumin treatment protects rat retinal nemons against excitotoxicity effect on A-methyl-D -aspartate-induced intracellular Ca + increase. Exp. Brain Res. 2005,167, 641-648. 

The concept of excitotoxicity was proposed as early as 1957 by Lucas and Newhouse [62] who demonstrated that glutamate is toxic for retinal cells. In the 70s, the work published by Olney and Ho [63] proved that glutamate and similar compounds administered to rodents during the neonatal period lead to acute neurodegeneration in retinal neurones and periventricular structures. Excitotoxicity is related to an excessive flow of calcium into the neurone resulting from an overstimulation due to different categories of excitatory amino acid receptors [64]. An excess of neurotransmitters produces several effects ... 

---