June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
The MDM2 T309G mutation in primary human retinal epithelial cells enhances experimental proliferative vitreoretinopathy
Author Affiliations & Notes
  • wenyi wu
    schepens eye research insititution, Boston, Massachusetts, United States
  • yajiang duan
    schepens eye research insititution, Boston, Massachusetts, United States
  • gaoen ma
    schepens eye research insititution, Boston, Massachusetts, United States
  • Yewlin Chee
    schepens eye research insititution, Boston, Massachusetts, United States
  • Arif Samad
    Department of Ophthalmology and Visual Sciences, Vancouver, British Columbia, Canada
  • Jing Z Cui
    Department of Ophthalmology and Visual Sciences, Vancouver, British Columbia, Canada
  • Joanne A Matsubara
    Department of Ophthalmology and Visual Sciences, Vancouver, British Columbia, Canada
  • Shizuo Mukai
    schepens eye research insititution, Boston, Massachusetts, United States
  • Patricia A D'Amore
    schepens eye research insititution, Boston, Massachusetts, United States
  • Hetian Lei
    schepens eye research insititution, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   wenyi wu, None; yajiang duan, None; gaoen ma, None; Yewlin Chee, None; Arif Samad, None; Jing Cui, None; Joanne A Matsubara, None; Shizuo Mukai, None; Patricia D'Amore, None; Hetian Lei, None
  • Footnotes
    Support  EY012509
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5964. doi:
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      wenyi wu, yajiang duan, gaoen ma, Yewlin Chee, Arif Samad, Jing Z Cui, Joanne A Matsubara, Shizuo Mukai, Patricia A D'Amore, Hetian Lei; The MDM2 T309G mutation in primary human retinal epithelial cells enhances experimental proliferative vitreoretinopathy
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):5964.

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

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Abstract

Purpose : The murine double minute 2(MDM2), whose human homologue is also called HDM2, is a critical negative regulator of the p53 tumor suppressor and the G309 allele of singe nucleotide polymorphisms (SNPs) in the MDM2 promoter locus is associated with a higher risk of proliferative vitreoretinopathy (PVR). We have shown that the MDM2 T309G mutation created using clustered regularly interspaced short palindromic repeats (CRISPR)/associated endonuclease (Cas)9 enhances vitreous-induced expression of MDM2 and survival of primary human primary retinal pigment epithelial (hPRPE) cells. The goal of this project is to determine whether this MDM2 mutation contributes to the development of experimental PVR.

Methods : Human vitreous from PVR patients (HV) was used to treat the hPRPE cells with MDM2 T309T or T309G, and the expression of MDM2 and p53 in the treated cells was examined by western blot. The vitreous-induced cellular responses such as contraction were assessed, PVR was evaluated by intravitreal injection of the hPRPE cells with MDM2 T309T or T309G into rabbit eyes.

Results : Western blot analysis indicated that HV enhanced a increase (1.7 ± 0.2 fold) in MDM2 and a significant decrease in p53 in the PRPE cells with the MDM2 T309G compared to those with MDM2 T309T. In addition, we found that HV promoted cell contraction in the PRPE cells with the cells expressing MDM2 T309G contracting more than cells with MDM2 T309T. Furthermore, MDM2 T309G enhanced the development of PVR in the rabbit model.

Conclusions : The MDM2 SNP G309 contributes to the development of experimental PVR.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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