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K. M. Hatzopoulos, K. A. Vessey, M. M. Ward, J. L. Wilkinson-Berka, A. G. Miller, R. Heine, E. L. Fletcher; Retinal Dysfunction in an Animal Model of Retinopathy of Prematurity. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3124.
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Retinopathy of prematurity (ROP) is characterized by vascular, glial and neuronal pathology. Premature infants exposed to high level of oxygen later develop abnormal angiogensis which can lead to visual impairment. We evaluated the loss of retinal function in a rat model of ROP and investigated the benefits of treatments that target the renin-angiotensin system.
Oxygen-induced retinopathy (OIR), a model of ROP, was induced by exposing newborn Sprague-Dawley rats to 80% oxygen until postnatal day 11 (P11) and then room air until P18. Control animals were exposed to room air for the entire duration. Control and ROP rats either received (1) no treatment (n=10-12), (2) AT1-receptor antagonist, valsartan (4-40 mg/kg/day intraperitoneal; n=10 per group) or (3) prorenin receptor inhibitor, handle region peptide (HRP; 0.1 mg/kg/day miniosmotic pump; n=10-12) from P11-P18. Retinal function was assessed at P18 in all groups using paired-flash electroretinography (ERG) over high light intensities (1.5-2.0 log cd-s.m(-2)) to isolate rod and cone responses. Vascular change was evaluated by counting blood vessel profiles in paraffin embedded and H&E stained sectioned from all groups.
Treatment with both valsartan and prorenin receptor inhibitor reduced retinal angiogenesis in ROP. Retinal function was significantly reduced in all rats with ROP. We observed a significant reduction in the amplitude of the rod photoreceptor response (PIII) in rats with ROP compared with controls. Rod post-receptoral responses, including the amplitude of the PII and oscillatory potentials, were also reduced in rats with ROP. Cone post-receptoral responses were also significantly reduced in all rats with ROP. Although treatment with the AT1-receptor antagonist, valsartan or the prorenin receptor inhibitor reduced angiogenesis, there was no protective effects on neural function.
Our results indicate that exposure to high-oxygen during the early postnatal period leads to significant deficits in the function of both the rod and cone pathways. In addition, treatments that prevent pathological angiogenesis do not necessarily prevent retinal dysfunction. Further work is required to understand the underlying mechanisms for neural dysfunction during ROP.
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