The goal of this project is to elucidate the role of glutathione (GSH) in the development of ocular surfacetissues. GSH is the most abundant cellular non-protein thiol and together with GSSG forms the major cellularredox buffer. Through redox modulation, GSH modifies the function of redox-sensitive proteins that are keyplayers of pathways controlling cell proliferation, migration, differentiation and apoptosis. Previous studies haveshown that GSH redox state represents a key metabolic switch during in vitro embryo development, and GSHis indispensable for early mouse development. The ocular surface is replete with GSH. Existing lines ofevidence suggest that GSH is actively synthesized during ocular morphogenesis. In addition, major signalingtransduction pathways that regulate the development of ocular surface tissues, including fibroblast growthfactor receptor (FGFR), Notch and canonical Wnt/?-catenin pathways, are targets of redox modulation. It istherefore hypothesized that: (1) GSH synthesis is essential for normal development of ocular surfacetissues; (2) GSH, through its redox modulation, regulates key signaling pathways during ocularmorphogenesis. This hypothesis will be tested by two Specific Aims: (1) characterize the ocular phenotype(s)of a mutant mouse line rendered incapable of GSH synthesis specifically inlineage cells that will commit exclusively to ocular surface development; (2) assess the changes in the activityof three aforementioned signaling pathways in mutant mice. The results derived from these studies willenhance our understanding of the process of eye development in greater molecular detail. Since theaforementioned signaling pathways are not restricted to the eye, the new knowledge derived from theproposed studies may have relevance and be extended to general embryogenesis and organogenesis.
The goal of this project is to elucidate the role of glutathione (GSH) in the development of ocular surfacetissues. GSH is the most abundant cellular non-protein thiol and together with GSSG forms the major cellularredox buffer. We propose studies that will test the hypotheses that: (1) GSH synthesis is essential fornormal development of ocular surface tissues; (2) GSH; through its redox modulation; regulates keysignaling pathways during ocular morphogenesis.
| Monte, Andrew A; Anderson, Peter; Hoppe, Jason A et al. (2015) Accuracy of Electronic Medical Record Medication Reconciliation in Emergency Department Patients. J Emerg Med 49:78-84 |
| Monte, Andrew A; Heard, Kennon J; Hoppe, Jason A et al. (2015) The accuracy of self-reported drug ingestion histories in emergency department patients. J Clin Pharmacol 55:33-8 |
| Monte, Andrew A; Heard, Kennon J; Campbell, Jenny et al. (2014) The effect of CYP2D6 drug-drug interactions on hydrocodone effectiveness. Acad Emerg Med 21:879-85 |
