James and Jean Culver Vision Discovery Institute

Sylvia Smith, Ph.D.

Contact info:
Dr. Smith's departmental website

Voice: 706.721.7392
Fax:    706.721.6839


Background & Research Emphasis:
The research in my lab focuses on normal functioning of the mammalian retina and on the consequences on retinal health when those functions go awry. We are interested in diabetic retinopathy and glaucoma, two diseases in which retinal ganglion cells die via an apoptotic (programmed cell death) mechanism. We have models for this phenomenon, both in cell culture and in mouse models. For diabetic retinopathy, we use the Ins2Akita mouse and the streptozotocin-induced model of diabetes. Our studies have focused on a unique pharmacologically-defined, non-opioid protein termed sigma (?) receptor. We have shown that ligands for ?R1 have robust neuroprotective properties. Recently, we characterized the retinal phenotype in mice that lack ?R1. We have observed a late onset retinal degeneration in these mice that reflects inner retinal dysfunction. In addition to these studies of neuroprotection, we have an interest also in transport of the vitamin folate, which is needed for synthesis of DNA and RNA. When folate levels are decreased, the levels of the amino acid homocysteine can increase. Related to our investigations of folate transport is a project that investigates the effects of excess homocysteine on the retina. We have data obtained in a mouse model of hyperhomocysteinemia (cystathionine ?-synthase deficient mouse) that shows loss of retinal ganglion cells under modest hyperhomocysteinemic conditions. We are now investigating a second mouse with a mutation of the methylene tetrahydrofolate reductase gene that also has excess homocysteine to elucidate the role of this amino acid in retinal disease.