July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Sumoylation Regulation of Lens Cataractogenesis
Author Affiliations & Notes
  • David W Li
    Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen Universit, Guangzhou City, China
    The Center for VIrology, University of Nebraska-Lincoln, Lincoln, Nebraska, United States
  • Yunfei Liu
    Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen Universit, Guangzhou City, China
  • Jia-Wen Xiang
    Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen Universit, Guangzhou City, China
    College of Life Sciences, Hunan Normal University, Changsha, Hunan, China
  • xiaodong Gong
    Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen Universit, Guangzhou City, China
  • Fangyuan Liu
    Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen Universit, Guangzhou City, China
  • Jia-Ling Fu
    Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen Universit, Guangzhou City, China
  • Yuan Xiao
    Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen Universit, Guangzhou City, China
    College of Life Sciences, Hunan Normal University, Changsha, Hunan, China
  • Ling Wang
    Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen Universit, Guangzhou City, China
  • Yizhi Liu
    Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen Universit, Guangzhou City, China
  • Footnotes
    Commercial Relationships   David Li, None; Yunfei Liu, None; Jia-Wen Xiang, None; xiaodong Gong, None; Fangyuan Liu, None; Jia-Ling Fu, None; Yuan Xiao, None; Ling Wang, None; Yizhi Liu, None
  • Footnotes
    Support  National Natural Science Foundation of China, 81570824, 81770910, 81500738, 81500707, and 81700821
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1130. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      David W Li, Yunfei Liu, Jia-Wen Xiang, xiaodong Gong, Fangyuan Liu, Jia-Ling Fu, Yuan Xiao, Ling Wang, Yizhi Liu; Sumoylation Regulation of Lens Cataractogenesis. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1130.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Our recent studies revealed that sumoylation is necessary to activate the p32 Pax6, the shortest isoform of Pax6, the master regulator for eye and brain development (Yan et al. 2010. PNAS). Moreover, our studies further revealed that sumoylation plays an important role in regulating lens differentiation (Qong et al. 2014. PNAS). Here we demonstrate that sumoylation has important functions in regulating cataractogenesis.

Methods : SUMO1(-/-) knockout mice and vimentin E151K mice were established with CRISPR-CAS9 technology. Adult mouse lenses from wild type and SUMO1 knockout mice were irradiated with UVA followed by culturing at media 199. RNAseq, QRT-PCR, Western blot analysis and immunocytochemistry were used to analyze gene expression. CellTitle-Glo assay, Hoechst staining and cell flow cytometry were used for apoptosis analysis.

Results : After UVA irradiation, SUMO1(-/-) lenses develop cataract in 2-4 hours during the post-irradiation culture, while the wild type lenses remain transparent for up to 10 hours. After 10 hours post UVA irradiation, the wild type mouse lens also began to develop cataract. At the molecular level, caspase-3 in the SUMO1(-/-) lens was completely activated after 2-hour culture post-UVA irradiation while in the wild type lens majority of the caspase-3 exists in pro-caspase-3 and partially processed caspase-3. Co-IP linked Western blot analysis revealed that caspase-3 was sumoylated in the wild type animal but not in the SUMO1 (-/-) mouse lenses. UVA irradiation also significantly activates p53, and upregulates caspase-8 but down regulates Bcl-2 in the SUMO1(-/-) lens in comparison with wild type lenses. In addition, creation of a novel sumoylation site in vimentin (the E151K mutant) causes cataract through blockage of oligomerization of the vimentin monomers.

Conclusions : SUMO1 regulates both extrinsic and intrinsic apoptotic pathways through controlled caspase-3 activation. Under stress condition, lack of SUMO1 greatly promotes activation of Caspase-3, and both the extrinsic and intrinsic apoptotic pathways. Sumoylation of the E151K mutant vimentin blocks normal polymerization, causing cataractogenesis (Supported by grants from National Natural Science Foundation of China, 81570824, 81770910, 81500738, 81500707, and 81700821 as well as the Fundamental Funds from the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University).

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×