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Mohamed G. Qaddoumi, Anna Polosa, Sylvain Chemtob, Pierre Lachapelle; Role of 20-Hydroxyeicosatetraenoic Acid in a Rat Model of Oxygen-induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1215.
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© ARVO (1962-2015); The Authors (2016-present)
20-Hydroxyeicosatetraenoic Acid (20-HETE), an arachidonic acid metabolite, is a vasoconstrictor eicasanoid shown previously to induce both ischemia and oxidative stress in brain and coronary vasculature, both of which were reversed using an inhibitor of 20-HETE. The purpose of this study was to investigate if inhibition of 20-HETE could alleviate the functional and structural abnormalities observed in a rat model of oxygen-induced retinopathy.
Normal and oxygen-induced retinopathy (exposed to 80% oxygen) Sprague-Dawley (SD) juvenile rats were chronically injected intraperitoneally with either 2 mg/kg HET0016 (20-HETE inhibitor) or vehicle (DMSO) from P6-14. The effects of HET0016 on retinal function were evaluated via scotopic (intensity: -6.3 to 0.6 log cd.sec.m-2; 12 hours dark adaptation) and photopic (intensity: 0.9 log cd.sec.m-2; background: 30 cd.m-2) electroretinography (ERG) in both P30 and P60. The effect of HET0016 on retinal structure was evaluated using whole retina histology on both P30 and P60.
Intraperitoneal injection of HET0016 to hyperoxic rats did not significantly affect the scotopic a- and b-wave amplitudes compared to hyperoxic rats injected with DMSO. However, both cohorts of hyperoxic rats had diminished scotopic and photopic b-wave amplitudes (averaging at 40% and 57% less for both) compared to control rats exposed to normal air at both P30 and P60. Photopic b-wave amplitudes of hyperoxic rats injected with HET0016 were higher at both P30 (17% higher) and P60 (15.5%) than in their hyperoxic cohorts injected with DMSO, though this was not significant enough. When comparing the ratio of scotopic b-wave amplitudes of HET0016 injected rats versus DMSO injected rats in both normoxic (0.81 and 0.90) and hyperoxic (1.00 and 1.06) cohort rats in both P30 and P60, a noticeable increase of 19% and 17% is seen in favor of HET0016 injected hyperoxic rats, respectively. A similar observation was noticeable with photopic b-wave amplitudes as well.
Our findings suggest that inhibition of 20-HETE may have some minor protective effects on retinal function in hyperoxic rats by attenuating the decrease in both the scotopic and photopic b-wave amplitudes. Whether these findings are due to the vasodilator and anti-oxidant properties of HET0016 on the ischemic phase of retinopathy or its anti-angiogenic effects on the neovascularization phase of retinopathy remain to be elucidated. It would be interesting to observe if inhibition of 20-HETE has any beneficial effects on other models of retinopathy, such as light-induced or diabetic retinopathy, andwhether this protective effects could be of greater impact if the drug was delivered topically or intravitreally.
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