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Research Project Description:
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Homocysteine is a non-proteinogenic amino acid that is known to cause cardiovascular and neurodegenerative complications; however, the neurotoxic effects of homocysteine on the retina are less studied. There is clinical literature to suggest a correlation between elevated homocysteine levels and visual disorders such as glaucoma and diabetic retinopathy; therefore, our laboratory has used a basic science approach to investigate the damaging potential of homocysteine on the cells of the retina, with a focus on retinal ganglion cells.
Our lab has previously published on the toxic potential of homocysteine to retinal ganglion cells in in vitro model systems. I am interested in using primary ganglion cell culture to further explore the mechanisms by which homocysteine is toxic to these cells. While the in vitro system affords direct manipulation of the experimental system and control of extraneous variables, it does not mimic perfectly the physiological consequences of endogenous elevations in homocysteine. A mouse deficient in cystathionine beta-synthase (CBS) that has an endogenous elevation in homocysteine has been developed and a colony has been established in our lab. I am also interested in using this mouse model to determine the effects of elevated plasma levels of homocysteine on the retina, and in particular, retinal ganglion cells.
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Papers / Presentations:
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Hatanaka T, Haramura M, Fei YJ, Miyauchi S, Bridges CC, Ganapathy PS, Smith SB, Ganapathy V, Ganapathy ME. Transport of amino acid-based prodrugs by the Na+- and CI(-) -coupled amino acid transporter ATB0, + and expression of the transporter in tissues amenable for drug delivery. J Pharmacol Exp Ther. 2004;308(3):1138-1147
Ganapathy PS, Farrow JJ, Dun Y, et al. Localization of a New Proton-Coupled Folate Transporter (PCFT) in Retina. ARVO, Fort Lauderdale, FL. April 27, 2008 |