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K. Renganathan, J. Gu, R. Collier, C. Romano, R. G. Salomon, M. Rayborn, J. G. Hollyfield, J. W. Crabb; Drugs That Prevent Retinal Light Damage Impact CEP Biomarker Levels. Invest. Ophthalmol. Vis. Sci. 2009;50(13):681.
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To determine whether carboxyethylpyrrole (CEP) biomarker concentrations change in rats treated with drugs that prevent light-induced retinopathy. CEP adducts are oxidative protein modifications derived from docosahexaenoate-containing lipids and that increase in rodent retina upon intense light exposure. CEP adducts are elevated in human age-related macular degeneration (AMD) Bruch’s membrane and mean CEP adduct and autoantibody levels are elevated in AMD plasma. AL-8309A is a serotonin 5-HT1A agonist that prevents retinal light damage in rats.
Albino rats were dark adapted prior to blue light exposure (3.1 X 103 mW/cm2, =465 nm) for 6 h. Control rats were maintained in normal cyclic light. Rats were injected subcutaneously 3x with 10 mg/kg AL-8309A (2 days, 1 day and 0 hours) before light exposure. Animals were sacrificed immediately following light exposure and retinas and plasma were collected, protected with antioxidants and frozen at -80ºC until analysis. Western analysis with densitometry and ELISA were used to quantify CEP biomarkers in rat retinal homogenates and plasma, respectively. CEP adducts were localized in rat ocular tissues by immunocytochemistry.
Western analysis showed that CEP adducts are elevated in rat retina and plasma following in vivo blue light exposure and that pretreatment with AL-8309A reduced CEP immunoreactivity ~40% in retina (n > 70 rats) and ~30% in plasma (n = 22 rats). Pretreatment with AL-8309A also reduced CEP autoantibody levels over 30% relative to vehicle + light treated animals (n = 22 rats). Immunocytochemical analyses were consistent with greater CEP immunoreactivity in retina after light exposure and less after drug + light treatment.
This study supports CEP adducts and autoantibodies as potential biomarkers for monitoring the efficacy of therapeutic agents that impact cellular defense against oxidative stress.
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