The investigator has developed a reasonable model which couples directed current to fluid transport, creating an internal circulatory system in the lens. The convection of nutrients along intercellular clefts to mature fiber cells is driven by the active transport of proteins from surface cells thereby maintaining homeostasis in the mature fiber cells. The investigator suggests that oxidative damage over time compromise the integrity of peripheral proteins resulting in the loss of homeostasis in the central mature fibers. Thus, Specific Aim 1 will identify membrane transport proteins damaged by oxidation and the subsequent effect on circulation will be followed.
Specific Aim 2 is founded on the basis that the lens is physiologically regulated with the stated goal to determine the regulatory effects on lens membrane transport proteins via activation of adrenergic, purinergic, muscarinic and insulin receptors. As fiber cell gap junctions are an essential component of the circulation model, Specific Aim 3 deals with the functional role of the fiber cell gap junction proteins, Cx46 and Cx50.
| Kumari, Sindhu; Gao, Junyuan; Mathias, Richard T et al. (2017) Aquaporin 0 Modulates Lens Gap Junctions in the Presence of Lens-Specific Beaded Filament Proteins. Invest Ophthalmol Vis Sci 58:6006-6019 |
| Gao, Junyuan; Sun, Xiurong; White, Thomas W et al. (2015) Feedback Regulation of Intracellular Hydrostatic Pressure in Surface Cells of the Lens. Biophys J 109:1830-9 |
| Liu, Ke; Lyu, Lei; Chin, David et al. (2015) Altered ubiquitin causes perturbed calcium homeostasis, hyperactivation of calpain, dysregulated differentiation, and cataract. Proc Natl Acad Sci U S A 112:1071-6 |
| Sindhu Kumari, S; Gupta, Neha; Shiels, Alan et al. (2015) Role of Aquaporin 0 in lens biomechanics. Biochem Biophys Res Commun 462:339-45 |
| Cheng, Catherine; Nowak, Roberta B; Gao, Junyuan et al. (2015) Lens ion homeostasis relies on the assembly and/or stability of large connexin 46 gap junction plaques on the broad sides of differentiating fiber cells. Am J Physiol Cell Physiol 308:C835-47 |
| Hall, James E; Mathias, Richard T (2014) The aquaporin zero puzzle. Biophys J 107:10-5 |
| Scheiblin, David A; Gao, Junyuan; Caplan, Jeffrey L et al. (2014) Beta-1 integrin is important for the structural maintenance and homeostasis of differentiating fiber cells. Int J Biochem Cell Biol 50:132-45 |
| Slavi, Nefeli; Rubinos, Clio; Li, Leping et al. (2014) Connexin 46 (cx46) gap junctions provide a pathway for the delivery of glutathione to the lens nucleus. J Biol Chem 289:32694-702 |
| Sellitto, Caterina; Li, Leping; Gao, Junyuan et al. (2013) AKT activation promotes PTEN hamartoma tumor syndrome-associated cataract development. J Clin Invest 123:5401-9 |
| Gao, Junyuan; Wang, Huan; Sun, Xiurong et al. (2013) The effects of age on lens transport. Invest Ophthalmol Vis Sci 54:7174-87 |
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