March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Role of 20-Hydroxyeicosatetraenoic Acid in a Rat Model of Oxygen-induced Retinopathy
Author Affiliations & Notes
  • Mohamed G. Qaddoumi
    Applied Therapeutics, Kuwait University School of Pharmacy, Kuwait, Kuwait
  • Anna Polosa
    Ophthal/Neurol-Neurosurgery, McGill Univ/Montreal Children's Hosp, Montreal, Quebec, Canada
  • Sylvain Chemtob
    Pediatrics & Pharmacology, Research Ctr/Hosp Ste Justine, Montreal, Quebec, Canada
  • Pierre Lachapelle
    Ophthal/Neurol-Neurosurgery, McGill Univ/Montreal Children's Hosp, Montreal, Quebec, Canada
  • Footnotes
    Commercial Relationships  Mohamed G. Qaddoumi, None; Anna Polosa, None; Sylvain Chemtob, None; Pierre Lachapelle, None
  • Footnotes
    Support  Reseau Vision AND NSERC
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 1215. doi:
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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)

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Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: retina • electroretinography: non-clinical • retinopathy of prematurity 

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