Silicone oil-induced ocular hypertension and glaucomatous neurodegeneration in mouse

  1. Jie Zhang
  2. Liang Li
  3. Haoliang Huang
  4. Fang Fang
  5. Hannah C Webber
  6. Pei Zhuang
  7. Liang Liu
  8. Roopa Dalal
  9. Peter H Tang
  10. Vinit B Mahajan
  11. Yang Sun
  12. Shaohua Li
  13. Mingchang Zhang
  14. Jeffrey L Goldberg
  15. Yang Hu  Is a corresponding author
  1. Stanford University School of Medicine, United States
  2. Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China

Abstract

Understanding the molecular mechanism of glaucoma and development of neuroprotectants are significantly hindered by the lack of a reliable animal model that accurately recapitulates human glaucoma. Here we sought to develop a mouse model for the secondary glaucoma that is often observed in humans after silicone oil (SO) blocks the pupil or migrates into the anterior chamber following vitreoretinal surgery. We observed significant intraocular pressure (IOP) elevation after intracameral injection of SO, and that SO removal allows IOP to return quickly to normal. This simple, inducible and reversible mouse ocular hypertension model shows dynamic changes of visual function that correlate with progressive RGC loss and axon degeneration. It may be applicable with only minor modifications to a range of animal species in which it will generate stable, robust IOP elevation and significant neurodegeneration that will facilitate selection of neuroprotectants and investigating the pathogenesis of ocular hypertension-induced glaucoma.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all the figures.

Article and author information

Author details

  1. Jie Zhang

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Liang Li

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Haoliang Huang

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Fang Fang

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Hannah C Webber

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Pei Zhuang

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Liang Liu

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Roopa Dalal

    Department of Ophthalmology, Stanford University School of Medicine, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Peter H Tang

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Vinit B Mahajan

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Yang Sun

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Shaohua Li

    Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Mingchang Zhang

    Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Jeffrey L Goldberg

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1390-7360
  15. Yang Hu

    Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, United States
    For correspondence
    huyang@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7980-1649

Funding

National Eye Institute (EY024932)

  • Yang Hu

National Eye Institute (EY023295)

  • Yang Hu

National Eye Institute (EY028106)

  • Yang Hu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#32093) of the Stanford University.

Reviewing Editor

  1. Jeremy Nathans, Johns Hopkins University School of Medicine, United States

Publication history

  1. Received: February 8, 2019
  2. Accepted: May 14, 2019
  3. Accepted Manuscript published: May 15, 2019 (version 1)
  4. Version of Record published: May 23, 2019 (version 2)

Copyright

© 2019, Zhang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jie Zhang
  2. Liang Li
  3. Haoliang Huang
  4. Fang Fang
  5. Hannah C Webber
  6. Pei Zhuang
  7. Liang Liu
  8. Roopa Dalal
  9. Peter H Tang
  10. Vinit B Mahajan
  11. Yang Sun
  12. Shaohua Li
  13. Mingchang Zhang
  14. Jeffrey L Goldberg
  15. Yang Hu
(2019)
Silicone oil-induced ocular hypertension and glaucomatous neurodegeneration in mouse
eLife 8:e45881.
https://doi.org/10.7554/eLife.45881

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