July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Persistent Choroidal Involution is p53-Dependent in Oxygen-Induced Retinopathy
Author Affiliations & Notes
  • Tianwei (Ellen) Zhou
    Medicine, McGill University, Montreal, Quebec, Canada
    Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Houda Tahiri
    Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Samy Omri
    Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Tang Zhu
    CHU Sainte-Justine, Montreal, Quebec, Canada
  • José Carlos Rivera
    Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Isabelle Lahaie
    Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Cheri Deal
    CHU Sainte-Justine, Montreal, Quebec, Canada
  • Stanley Nattel
    Medicine, McGill University, Montreal, Quebec, Canada
    Montreal Heart Institute, Montreal, Quebec, Canada
  • Patrick Hamel
    CHU Sainte-Justine, Montreal, Quebec, Canada
  • Sylvain Chemtob
    CHU Sainte-Justine, Montreal, Quebec, Canada
    Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships   Tianwei (Ellen) Zhou, None; Houda Tahiri, None; Samy Omri, None; Tang Zhu, None; José Rivera, None; Isabelle Lahaie, None; Cheri Deal, None; Stanley Nattel, None; Patrick Hamel, None; Sylvain Chemtob, None
  • Footnotes
    Support  CIHR MD-PhD scholarship; Fonds de recherche en ophtalmologie de l'Université de Montréal; Fonds Suzanne Véronneau-Troutman, Université de Montréal; Canadian Medical Hall of Fame Award
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2648. doi:
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      Tianwei (Ellen) Zhou, Houda Tahiri, Samy Omri, Tang Zhu, José Carlos Rivera, Isabelle Lahaie, Cheri Deal, Stanley Nattel, Patrick Hamel, Sylvain Chemtob; Persistent Choroidal Involution is p53-Dependent in Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2648.

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

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Abstract

Purpose : Retinopathy of prematurity (ROP), the most common cause of blindness in premature infants, has long been associated with pathologic retinal vasculature. However, recent studies reveal choroidal involution in adolescent patients formerly afflicted with ROP. We have recently demonstrated that choroidal thinning occurs early in retinopathy and persists into adulthood. Unlike retinal vessels, the damaged choroidal vasculature in ROP is incapably to regenerate. Herein, we investigated the molecular mechanism implicated in the lack of choroidal repair in ischemic retinopathy.

Methods : The oxygen-induced retinopathy (OIR) model was used. Newborn Sprague-Dawley (albino) or Long-Evans rats (pigmented) rats were placed under oxygen concentration which cycles at 50±1% or 10±1% every 24 hours (hr) from postnatal day (P) 0 to P14. On P14, all rats were returned to room air. Western blotting and qPCR were used to quantify protein and RNA abundances, respectively. The Dual-Luciferase® Reporter Assay System was used to confirm microRNA (miRNA)-mRNA interaction.

Results : We detected a substantial oxidative stress in retinal pigment epithelium (RPE) and choroidal tissue, accompanied by a drastic reduction in insulin-like growth factor 1 receptor (IGF1R), a critical player in post-injury revascularization. Tumor suppressor p53 down-regulates IGF1R in an miRNA-dependent manner. Luciferase reporter assay confirmed that Igf1r mRNA is a true target of the miRNA of interest. Interestingly, silencing p53 resulted in a decreased miRNA expression, and re-established IGF1R abundance that promoted choroidal regeneration.

Conclusions : Together, this study sets forth new mechanistic notion by uncovering the novel p53/ miRNA /IGF1R axis; timely intervention of this pathway facilitates healthy choroidal revascularization and can prevent further ischemic damage. Future investigations on anti-angiogenic miRNAs can better our understanding on degenerative choroidopathy, including geographic atrophy.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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