Abstract
Presentation Description :
Intercellular communication mediated by Cx46 and Cx50 gap junction (GJ) channels is central to the transport of ions in the lens and maintenance of lens transparency. The role of GJs in the development of age-related nuclear cataracts is less studied, and is the main focus of this talk. A key factor that influences senile cataract formation is the age-dependent decline in the levels of reduced glutathione (GSH) and associated cofactors in the lens nucleus.The presentation will examine the importance of GJ channels in the transport of molecules to the lens nuclues, including GSH and NADPH, a co-factor critical in redox reactions. Additionally, the role of GJ channels in the age-dependent shift to a more oxidized environment in the nucleus, thereby predisposing proteins to oxidative damage and nuclear cataract, will be examined . Electrophysiogical studies showing the extent of permeability of Cx46 and Cx50 to metabolites and biochemical studies examining the dependence of NADPH and glutathione levels in the nucleus on GJ channels will be presented. Using imaging and and mass spectrometry, the age-dpendent post-translational modifications (PTMs) of Cx46 and Cx50 in different regions of the lens will be identified. Whether accumulation of PTMs to Cx46 and Cx50 explains the abrupt age-dependent decline in reduced glutathione and NADPH levels in the lens nucleus will be discussed
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.