Uddin Md Imam, Jayagopal Ashwath, McCollum Gary W, Yang Rong, Penn John S
Department of Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee, United States.
Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd. Basel, Switzerland.
Invest Ophthalmol Vis Sci. 2017 Jul 1;58(9):3818-3824. doi: 10.1167/iovs.16-21187.
To demonstrate the utility of a novel in vivo molecular imaging probe, HYPOX-4, to detect and image retinal hypoxia in real time, in a mouse model of retinal vein occlusion (RVO).
Retinal vein occlusion was achieved in adult mice by photodynamic retinal vein thrombosis (PRVT). One or two major retinal vein(s) was/were occluded in close proximity to the optic nerve head (ONH). In vivo imaging of retinal hypoxia was performed using, HYPOX-4, an imaging probe developed by our laboratory. Pimonidazole-adduct immunostaining was performed and used as a standard ex vivo method for the detection of retinal hypoxia in this mouse RVO model. The retinal vasculature was imaged using fluorescein angiography (FA) and isolectin B4 staining. Retinal thickness was assessed by spectral-domain optical coherence tomography (SD-OCT) analysis.
By application of the standard ex vivo pimonidazole-adduct immunostaining technique, retinal hypoxia was observed within 2 hours post-PRVT. The observed hypoxic retinal areas depended on whether one or two retinal vein(s) was/were occluded. Similar areas of hypoxia were imaged in vivo using HYPOX-4. Using OCT, retinal edema was observed immediately post-PRVT induction, resolving 8 days later. Nominal preretinal neovascularization was observed at 10 to 14 days post-RVO.
HYPOX-4 is an efficient probe capable of imaging retinal hypoxia in vivo, in RVO mice. Future studies will focus on its use in correlating retinal hypoxia to the onset and progression of ischemic vasculopathies.
在视网膜静脉阻塞（RVO）小鼠模型中，证明新型体内分子成像探针HYPOX-4实时检测和成像视网膜缺氧的效用。
通过光动力视网膜静脉血栓形成（PRVT）在成年小鼠中实现视网膜静脉阻塞。在紧邻视神经乳头（ONH）处阻塞一条或两条主要视网膜静脉。使用我们实验室开发的成像探针HYPOX-4对视网膜缺氧进行体内成像。进行匹莫硝唑加合物免疫染色，并将其用作该小鼠RVO模型中检测视网膜缺氧的标准离体方法。使用荧光素血管造影（FA）和异凝集素B4染色对视网膜血管系统进行成像。通过光谱域光学相干断层扫描（SD-OCT）分析评估视网膜厚度。
通过应用标准离体匹莫硝唑加合物免疫染色技术，在PRVT后2小时内观察到视网膜缺氧。观察到的缺氧视网膜区域取决于阻塞的是一条还是两条视网膜静脉。使用HYPOX-4在体内对相似的缺氧区域进行了成像。使用OCT，在PRVT诱导后立即观察到视网膜水肿，8天后消退。在RVO后10至14天观察到名义上的视网膜前新生血管形成。
HYPOX-4是一种有效的探针，能够在RVO小鼠体内对视网膜缺氧进行成像。未来的研究将集中于其在将视网膜缺氧与缺血性血管病变的发生和进展相关联方面的应用。
