Glaucoma is one of the most important causes of blindness in human and dogs. Glaucoma is characterized by a progressive loss of retinal ganglion cells that is often associated with increased intraocular pressure and decreased retinal blood flow. In previous investigations, we found that changes in glutamate distribution occur selectively in damaged areas of retinas of dogs with primary glaucoma. This glutamate redistribution is consistent with high levels of extracellular glutamate (↑GluE) contributing to excitotoxic damage to neurons. In this dissertation, we used immunohistochemical methods to test three mechanisms by which this glutamate redistribution may occur in retinas from clinical cases of canine glaucoma. First, we tested if ischemia due to microvessel loss causes the changes in glutamate distribution. We found significantly lower microvessel density in damaged regions, consistent with ischemia occurring in canine glaucoma. Second, we tested if loss of glutamine synthetase induces the glutamate redistribution. We have found significantly decreased amounts of glutamine synthetase in areas with neuronal damage and glutamate redistribution, consistence with decreased glutamate synthetase contributing to glutamate redistribution. Third, leakage of glutamate from blood vessels from inflamed areas may lead to glutamate redistribution. We found that there is albumin leakage from blood vessels in damaged regions with other inflammatory indicators in those areas. The smaller size of glutamate suggests that it should also diffuse out of blood into the extracellular fluid of the retina even more readily than albumin. Increase leakiness of blood vessels in canine glaucoma is consistent with glutamate leakage contributing to glutamate redistribution. In conclusion, our results are consistent with all three mechanisms contributing to glutamate redistribution in canine glaucoma. The dissertation includes further discussion of more refined hypotheses of the mechanisms by which glutamate redistribution and neuronal damage may occur.