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Julie A Mocko, Deborah C Otteson, Yanhong Wei, Xanthi I Couroucli, Laura J Frishman; High dose vitamin A (HDVA) treatment increases revascularization and reduces neovascularization in a rat model of oxygen induced retinopathy (OIR).. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3449.
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© ARVO (1962-2015); The Authors (2016-present)
Postnatal hyperoxia disrupts retinal vascular development, causing subsequent retinal hypoxia, neural retinal injury, impaired function and neovascularization. This study examined age-related changes in vascular development, consequent changes in neural retinal thickness, and the impact of HDVA supplementation on these changes in a hyperoxic OIR rat model.
OIR was induced in Fisher 344 rats by exposure to 96±1% O2 from postnatal day P1 to P7, followed by a return to room air. Controls were raised in room air (AIR). All pups (n=3-5/age/group) received daily i.p. injections of either vehicle alone (VEH, corn oil, 33ml/kg), or with HDVA (10mg/kg) from P1 to P5. Vasculature in retinal flat mounts was labeled with isolectin GS-IB4. Retinal cross-sections (JB-4 embedded, 5µm) were stained with toludine blue. ImageJ and MATLAB were used to measure vascular coverage (%VC, vs. age-matched AIR), neovascularization (%NV, vs. VC), and retinal thickness (µm) for the central (C), middle (M) and peripheral (P) thirds of the retina. Statistical analysis used one-way ANOVA with post-hoc Tukey’s.
HDVA did not affect retinal VC or thickness in AIR. Hyperoxia caused severe vaso-obliteration, with total VC in OIR rats at 5-8% by P7 (p<0.0001). One week post-hyperoxia (P14), total VC increased in OIR rats to 26-39% (p<0.0001), but was not significantly different at P21 (22-37%). Regionally, at P21, VC (±SEM) in middle retina was greater in HDVA+OIR (51±7%) vs. VEH+OIR (26±12%) rats (p=0.03). At P21, NV in central retina was reduced in HDVA+OIR (14±6%) vs. VEH+OIR (39±8%) rats (p=0.026). Inner retinal thickness at P21 decreased with eccentricity (C, M, P) in AIR (173, 153, 128; ±5µm), but not OIR rats. In contrast, the inner retina showed marked thinning in OIR rats at P21 at all eccentricities in avascular regions (83±3µm, p≤0.001), and to a lesser extent in central and middle retina in vascularized regions (129±4µm, p≤0.012). HDVA+OIR rats had no avascular central regions, and overall had more vascular vs. avascular regions than VEH+OIR rats. VEH+OIR rats had no vascularized peripheral regions.
Hyperoxia caused severe vaso-obliteration, followed by vaso-proliferation resulting in incomplete VC and severe NV; HDVA treatment increased VC and reduced NV. OIR-mediated retinal thinning was most severe in avascular retinal regions.
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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