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Xiaohua Gong; Metabolites and homeostasis mediated by gap junction/connexin in vivo. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5220.
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© ARVO (1962-2015); The Authors (2016-present)
Presentation Description :
Mice with Gja3 gene knockout (Gja3 KO) develop variable nuclear cataracts between the C57BL/6J (B6) and 129SvJae (129) strain backgrounds. To investigate how lens transparency, metabolites and homeostasis are regulated by intercellular gap junction communication and genetic variances of different mouse strains, the metabolic profiles of lenses from different wildtype or mutant strain backgrounds were determined by Mass-spec analysis. Both the CP49 deletion in129 strain background and the B6-periaxin (prx) variant contribute to fiber cell morphogenesis including the surface topology, which was affected by Gja3 disruption, CP49 deletion and prx variances. Metabolite profiling revealed changes of antioxidants, glycolysis pathway intermediates and lipids compositions in Gja3-/- lenses of different strain backgrounds. Gja3 KO resulted in lower levels of glutathione (GSH) and cysteine while oxidized glutathione (GSSG) was fairly consistent. Homocysteine and methionine were decreased in KO lenses. However, glucose uptake and/or utilization appeared to be different in various strains. Sugar alcohols remained relatively constant despite varying glucose levels in the lens. Sphingolipid levels varied in different mouse strains. Combined effects of gap junctions, CP49 and prx-mediated cytoskeleton synergistically regulate the interdigitation structures of fiber cells, which influence lens transparency, homeostasis and metabolism. Changes in a large number of metabolites may affect the maintenance of lens fiber cell shape and surface topology. Taurine levels in B6 strain and mixed B6/129 strain remained higher, which might provide elevated antioxidant capacity in those strains with moderate nuclear cataracts. Levels of antioxidants and energy metabolism were clearly altered in KO lenses. The levels of lipids, particularly the sphingolipids and phospholipids, showed the most prominent changes affected by the strain variance and the loss of Cx46. These metabolic data will provide new testable hypotheses for examining the roles of gap junction communication in cataract formation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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