June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Quantitative and Qualitative Analysis of Retinal Hypoxia in a Mouse Model of Retinal Artery Occlusion (RAO)
Author Affiliations & Notes
  • MD Imam Uddin
    Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
  • Sara Jamal
    Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
  • Gary W. McCollum
    Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
  • John S Penn
    Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
  • Footnotes
    Commercial Relationships   MD Imam Uddin, None; Sara Jamal, None; Gary McCollum, None; John Penn, None
  • Footnotes
    Support  R01EY029693, R01EY023397, BrightFocus Foundation GRANT ID: M2019023
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 361. doi:
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      MD Imam Uddin, Sara Jamal, Gary W. McCollum, John S Penn; Quantitative and Qualitative Analysis of Retinal Hypoxia in a Mouse Model of Retinal Artery Occlusion (RAO). Invest. Ophthalmol. Vis. Sci. 2021;62(8):361.

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

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Abstract

Purpose : To demonstrate the quantitative and qualitative analysis of tissue hypoxia from a single retinal artery occlusion (RAO). Also, to demonstrate the utility of HYPOX-4 for early detection of retinal hypoxia in RAO in real time.

Methods : A major retinal artery was occluded in mice using laser-induced retinal artery occlusion using Rose Bengal. Real time imaging of the retinal hypoxia was achieved using HYPOX-4, a molecular imaging probe developed in our laboratory. Pimonidazole-adduct immunostaining was used as an ex vivo method to characterize retinal hypoxia in RAO. Retinal vasculature was imaged using fluorescein angiography (FA) and IB4 staining. Retinal tissue morphology was evaluated using spectral domain OCT (SD-OCT).

Results : Retinal hypoxia was observed in a mouse model of RAO within few hours of laser-induced retinal artery occlusion in mice. We also observed that occlusion of an artery near the optic disk caused a ‘pie-shaped’ tissue hypoxia covering about 1/8th of the entire retina. We also observed that occlusion of a vein in the same eye at about same distance from optic disk caused a ‘cascade-shaped’ tissue hypoxia covering about half of the entire retina (hemi-retinal ischemia). Retinal hypoxia was confirmed ex vivo using standard pimonidazole-adduct immunostaining method. Interestingly, we observed that the total hypoxic retina is about the same (~12% of the entire retina) from a single retinal artery occlusion compared to single retinal vein occlusion (RVO). This study provides the first quantitative and qualitative evidence of retinal hypoxia from single RAO and compared with single RVO in mice at early stage.

Conclusions : This study demonstrated the utility of a new hypoxia sensitive molecular imaging probe, HYPOX-4, to detect retinal hypoxia in RAO in real time at an early stage. This study also demonstrated that the pattern of tissue hypoxia is very different in RAO compared to RVO. Also, HYPOX-4 could be a powerful method to detect retinal hypoxia at an early stage that occurs in RAO and other vascular diseases.

This is a 2021 ARVO Annual Meeting abstract.

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