The long term goal of this project is to identify neruoprotective drugs that are effective in preventing the death of retinal ganglion cells in the mammalian retina. This objective will be realized by applying methods which tag retinal neurons with fluorescent markers that are specific for cell type and/or stress-induced proteins. Cell labelling procedures will be further developed for the automated determination of retinal cell body parameters by image analysis and by fluorescent-activated cell sorting/analysis. These methods will be applied to rodent models of induced (rat) congenital (mouse) ocular hypertension/glaucoma and hypoxia-induced retinopathy in the rat. The time course and pattern of pathologic changes in these models (intraocular pressure, electroretinogram, retinal ganglion cell death) will be determined to establish optimal models for drug testing. The above rat and mouse models of retinal neuropathy will then be used to evaluate neuroprotective agents for their activity to prevent or delay retinal cell death. The PI will evaluate receptor antagonists, calcium channel blockers, anti-apoptosis agents, antioxidants and oxyradical traps, antiproteases, and nitric oxide synthase inhibitors. The ultimate aims is the beneficial use of one or more of such agents as treatment in human optic neuropathies, particularly in glaucoma.