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Kendra Phillips, Tyler C. Kilburn, John S. Penn, Md Imam Uddin; Molecular Imaging of Retinal Hypoxia in Diabetic Mouse Models. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3732.
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© ARVO (1962-2015); The Authors (2016-present)
To longitudinally assess retinal hypoxia both in vivo and ex vivo in a mouse model of streptozotocin- (STZ) induced diabetic retinopathy (DR) using the molecular imaging probe HYPOX-4. DR is a vision-threatening condition affecting a large number of working-aged populations worldwide. The proliferative stage or PDR is the most devastating condition in DR, causing abnormal blood vessels growth called neovascularization (NV) in the inner retina. Although the pathogenesis of PDR is largely unknown, it is well accepted that hypoxia is a common contributor to the onset of NV.
HYPOX-4 is a new molecular imaging probe, used in this study to detect retinal hypoxia in diabetic mice. To induce diabetes, mice were injected with streptozotocin (STZ) and were monitored for hypoxia for 9 months after diabetes induction using HYPOX-4. ImageJ software was used to quantitatively measure the retinal hypoxia computationally and compared with control pimonidazole-adduct immunostaining. IB4 and collagen-IV co-immunostaining was used to analyze the retinal vascular structures. SD-OCT was used to monitor retinal thickness in diabetic retinas and compared with age-matched controls. Leukostasis was monitored using concanavalin A perfusion labeling of the leukocytes. Fluorescein angiography was used to measure vascular permeability in the retina.
Using pimonidazole-adduct immunostaining, we observed that healthy normal retina is physiologically hypoxic; however, the occurrence of retinal hypoxia in the diabetic retina is elevated compared to healthy controls, which can be detected in vivo using HYPOX-4. We also observed HYPOX-4 accumulation in the photoreceptor layer, which might be due to STZ-induced oxidative damage to the photoreceptor layer. The elevated HYPOX-4 fluorescence in the diabetic retina was not associated with capillary dropout; retinal hypoxia peaked at 2 months post-diabetes induction in these mouse retinas.
In summary, retinal hypoxia was detected and imaged using HYPOX-4 in STZ-induced mouse model of diabetic retinopathy. HYPOX-4 is a clinically relevant, non-toxic molecular imaging probe to detect retinal hypoxia in vivo. Keywords: HYPOX-4, diabetic retinopathy, molecular imaging, streptozotocin.
This is a 2020 ARVO Annual Meeting abstract.
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