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Marina Garcia Garrido, Jürgen Haller, Melanie Hugger, Jochen Huber, Nina Zippel, Rolf Herrmann; Early and late structural and functional findings of the Oxygen-Induced Retinopathy (OIR) mouse model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3446.
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© ARVO (1962-2015); The Authors (2016-present)
Ischemia-induced hypoxia is the common hallmark of retinal diseases such as Retinopathy of Prematurity (ROP), Diabetic Retinopathy (DR) or Retinal Vein Occlusion (RVO). In this study, we assessed morphological and functional hypoxia-derived changes in an OIR mouse model at both early (P17) and late stages (up to P80).
Pups were exposed to a 75% oxygen atmosphere from postnatal day (P) 7 to P12 and returned to room air at P12 to induce retinal revascularization. At P17, mice were anesthetized and subjected to en face retinal imaging, optical coherence tomography (OCT) and fluorescence angiography. Afterwards, in a subset of animals, eyes were enucleated and studied immunhistochemically. The rest of the animal cohort was maintained until P80. At this age, rod- and cone-driven functional responses as well as ganglion cell activity were assessed by means of electroretinography (ERG) and pattern-electroretinography (pERG), respectively. In addition, integrity of retinal structure and layering was later studied at P60 and P80. Subsequently, retinal ganglion cells were stained and Brn3a-positive cells were quantified.
At P17, avascular areas as well as intravitreal tufts were visualized in vivo. At later stages, fluorescein angiograms revealed a fully revascularized retina, however, intravitreal tufts were still visible. Additionally, a decrease of ERG response amplitudes as well as light sensitivity was detected. PERG measurements further showed a decline in ganglion cell function which correlated well with the reduction of the retinal thickness measured by OCT and the number of Brn3a-positive cells found in comparison to age-matched controls.
Despite revascularization processes that typically take place after exposure to high amounts of oxygen in this mouse model, structural changes in the main retinal vessels persist and may cause further functional impairments in addition to hypoxia at late timepoints. In addition, retinal cells, especially ganglion cells remain damaged over time. In this context, this study provided evidence that for the treatment of OIR, antiangiogenic agents are not sufficient to address the neuronal component of the disease.
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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