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.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences A Study Section (VISA)
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Mount Sinai School of Medicine
Schools of Medicine
New York
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Danias, John; Shen, Fran; Kavalarakis, Manolis et al. (2006) Characterization of retinal damage in the episcleral vein cauterization rat glaucoma model. Exp Eye Res 82:219-28
Gerometta, Rosana; Podos, Steven M; Candia, Oscar A et al. (2004) Steroid-induced ocular hypertension in normal cattle. Arch Ophthalmol 122:1492-7
Shen, Fran; Chen, Bin; Danias, John et al. (2004) Glutamate-induced glutamine synthetase expression in retinal Muller cells after short-term ocular hypertension in the rat. Invest Ophthalmol Vis Sci 45:3107-12
Danias, John; Lee, Kevin C; Zamora, Maria-Florencia et al. (2003) Quantitative analysis of retinal ganglion cell (RGC) loss in aging DBA/2NNia glaucomatous mice: comparison with RGC loss in aging C57/BL6 mice. Invest Ophthalmol Vis Sci 44:5151-62
Danias, John; Kontiola, Antti I; Filippopoulos, Theodoros et al. (2003) Method for the noninvasive measurement of intraocular pressure in mice. Invest Ophthalmol Vis Sci 44:1138-41
Danias, John; Shen, Fran; Goldblum, David et al. (2002) Cytoarchitecture of the retinal ganglion cells in the rat. Invest Ophthalmol Vis Sci 43:587-94
Goldblum, David; Kontiola, Antti Ilmari; Mittag, Thom et al. (2002) Non-invasive determination of intraocular pressure in the rat eye. Comparison of an electronic tonometer (TonoPen), and a rebound (impact probe) tonometer. Graefes Arch Clin Exp Ophthalmol 240:942-6
Bayer, A U; Danias, J; Brodie, S et al. (2001) Electroretinographic abnormalities in a rat glaucoma model with chronic elevated intraocular pressure. Exp Eye Res 72:667-77
Kontiola, A I; Goldblum, D; Mittag, T et al. (2001) The induction/impact tonometer: a new instrument to measure intraocular pressure in the rat. Exp Eye Res 73:781-5
Bayer, A U; Neuhardt, T; May, A C et al. (2001) Retinal morphology and ERG response in the DBA/2NNia mouse model of angle-closure glaucoma. Invest Ophthalmol Vis Sci 42:1258-65

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