June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Functional interaction between connexin 46 and periaxin in cataractogenesis
Author Affiliations & Notes
  • Xiaohua Gong
    School of Optometry, University of California Berkeley, Berkeley, California, United States
  • Vasantha Rao
    Department of Ophthalmology, Duke University School of Medicine, Durham, North Carolina, United States
  • Chun-hong Xia
    School of Optometry, University of California Berkeley, Berkeley, California, United States
  • Footnotes
    Commercial Relationships   Xiaohua Gong None; Vasantha Rao None; Chun-hong Xia None
  • Footnotes
    Support  NIH Grant EY013849
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 19. doi:
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    • Get Citation

      Xiaohua Gong, Vasantha Rao, Chun-hong Xia; Functional interaction between connexin 46 and periaxin in cataractogenesis. Invest. Ophthalmol. Vis. Sci. 2022;63(7):19.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To test a hypothesis that Periaxin (Prx) gene variant of 129 mouse strain background acts as a gain-of-function variant to facilitate severe nuclear cataract in connexin 46 knockout (Cx46KO) lenses by characterizing Prx-Cx46 double knockout (DKO) lens phenotypes. To determine the underlying cellular mechanism for functional association between connexin 46 and periaxin in lens homeostasis, stiffness and cataract formation.

Methods : Biochemical approaches including western blotting and morphological tools including laser confocal microscopic imaging were used to characterize and compare the molecular and cellular changes among lenses of wild-type, Cx46KO at different strain backgrounds and the Prx-Cx46 DKO mice in vivo. Prx gene variances were characterized in cultured cells in vitro.

Results : Severe nuclear cataracts in Cx46KO lenses were associated with the presence of highly expressed 129-periaxin proteins that were colocalized with F-actin in protrusions in lens fiber cells. The presence of 129-periaxin appeared to be associated with increased lens stiffness. Prx-Cx46 DKO at 129 strain background developed mild cataract that was similar to mild cataract in Cx46KO at C57BL/6J background, which expressed a low level of Prx variant in lens fibers.

Conclusions : Mild cataracts in DKO lenses suggest that a loss of periaxin significantly attenuate the development of severe nuclear cataracts in Cx46KO lenses at 129 strain background and 129-Prx gene acts as a gain-of-function variant to facilitate cataractogenesis caused by increased calcium levels in Cx46KO lenses. This result further indicates that both Cx46-mediated cell communication and Prx-mediated membrane-cytoskeletal complex regulate the calcium homeostasis in the lens fibers.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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