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Justin Wanek, Pang-yu Teng, Norman P Blair, Mahnaz Shahidi; Effect of Increased Vascular Endothelial Growth Factor on Inner Retinal Oxygen Delivery and Metabolism in Rats. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2098.
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Increased vascular endothelial growth factor (VEGF) promotes angiogenesis and vascular permeability and plays an important role in development of retinal pathologies. Accordingly, anti-VEGF agents are an optimal treatment for neovascular aged-related macular degeneration and diabetic retinopathy. The purpose of this study is to report the effect of increased VEGF on inner retinal oxygen delivery (DO2_IR) and oxygen metabolism (MO2_IR) in rats.
Retinal vascular oxygen tension (PO2) and blood flow were measured in both eyes of 6 rats under systemic normoxia, one day following intravitreal injection of VEGF in one eye (study) and balanced salt solution in the fellow eye (control). Retinal vascular PO2 was measured in major retinal arteries (PO2A) and veins (PO2V) by phosphorescence lifetime imaging. Arterial (O2A) and venous (O2V) oxygen contents were calculated from these measurements using the hemoglobin dissociation curve. Venous blood velocity (V) was measured by fluorescent microsphere imaging and venous diameter (D) was obtained by red-free retinal imaging. DO2_IR was determined from the product of total retinal blood flow (F = πD2V/4) and O2A, while MO2_IR was calculated from the product of F and arteriovenous oxygen content difference (O2A - O2V). Retinal oxygenation parameters were compared between study and control eyes using paired Students t-test.
Mean PO2V and O2V were significantly higher in study eyes compared to control eyes (p ≤ 0.04), while both mean PO2A and O2A were not significantly different between study and control eyes (p ≥ 0.67). Mean D was significantly higher in study eyes (p = 0.01) and mean V was similar between study and control eyes (p = 0.61). Consequently, F was significantly higher in study eyes compared to control eyes (p = 0.02). Mean DO2_IR in study eyes (1531 ± 651 nLO2 /min, N = 6) was significantly higher than in control eyes (1026 ± 368 nLO2/min, N = 6) (p = 0.03), while mean MO2_IR was not significantly different between study eyes (555 ± 179 nLO2/min) and control eyes (499 ± 129 nLO2/min) (p = 0.36).
Administration of VEGF resulted in increased F and DO2_IR due to vasodilation, but did not affect MO2_IR. These findings may have implications in the pathophysiology and treatment of retinal diseases associated with hypoxia and increased VEGF production.
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