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Md Imam Uddin, Ashwath Jayagopal, Gary W. McCollum, John S Penn; In Vivo Molecular Imaging of Retinal Hypoxia in a Mouse Model of Laser-induced Retinal Vein Occlusion (RVO). Invest. Ophthalmol. Vis. Sci. 2017;58(8):3665. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To demonstrate the utility of a new in vivo molecular imaging probe, HYPOX-4, for early detection of retinal hypoxia in a mouse model of retinal vein occlusion (RVO). This method will assist early detection of retinal hypoxia in real time and will facilitate studying the pathogenesis of RVO.
Induction of RVO was achieved in mice using photodynamic retinal vein thrombosis (PRVT) of major retinal vein(s) close to the optic disk. In vivo imaging of the retinal hypoxia was performed using a new molecular imaging probe, HYPOX-4, that was developed by our laboratory. Pimonidazole-adduct immunostaining was used as an ex vivo method for detecting retinal hypoxia in RVO mice. Retinal vasculature was imaged using fluorescein angiography (FA) and IB4 staining. Retinal tissue morphology was assessed using spectral domain OCT (SD-OCT).
Within a few hours of post-PRVT in mice, we observed significant changes in retinal hypoxia as determined by the pimonidazole-adduct immunostaining method. This method also showed that the extent of retinal hypoxia depends on the number of retinal veins occluded. After photocoagulation, the occluded veins reopened within one week as determined by FA, and neovascularization (NV) was observed at 10-14 days post-PRVT. HYPOX-4-dependent in vivo imaging showed retinal hypoxia in RVO mice during this period. This study provides the first qualitative and quantitative evidence of retinal hypoxia in RVO mice at early stages of vein occlusion.
This study demonstrated the utility of a new hypoxia sensitive molecular imaging probe, HYPOX-4, in RVO mice at an early stage before the onset of NV. HYPOX-4 could be a powerful predictive biomarker for the retinal NV that occurs in RVO and other vasculopathies. This study showed acute changes in retinal oxygen tension precede and may initiate vascular complications including NV in RVO mice.
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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