title: Changes in Retinal N-Acylethanolamines and their Oxylipin Derivatives During the Development of Visual Impairment in a Mouse Model for Glaucoma.
abstract: Neurons are especially susceptible to oxidative damage, which is increasingly implicated in neurodegenerative disease. Certain N-acylethanolamines (NAEs) have been shown to protect neurons from oxidative stress. Since glaucoma may be considered a neurodegenerative disorder and the survival of retinal neurons could also be influenced by N-acylethanolamines, our goal was to quantify changes in certain N-acylethanolamine species and their oxylipin derivatives in the retina of a mouse model for glaucoma. We also sought to identify relationships between these and parameters of glaucoma disease development, specifically intraocular pressure, visual acuity, and contrast sensitivity. Five N-acylethanolamine species and three NAE oxylipin derivatives were quantified in retina from young and aged DBA/2Crl mice. N-Acylethanolamines and NAE-oxylipins in retinal extracts were quantified against deuterated standards by isotope dilution gas chromatography-mass spectrometry. Levels (nmol/g dry weight) of N-arachidonoylethanolamine (anandamide; NAE 20:4) were significantly (p = 0.008) decreased in aged (2.875 ± 0.6702) compared to young animals (5.175 ± 0.971). Conversely, the anandamide oxylipin, 15(S)-HETE ethanolamide (15(S)-HETE EA), was significantly (p = 0.042) increased in aged (0.063 ± 0.009) compared to young animals (0.039 ± 0.011). Enzymatic depletion of the anandamide pool by 15-lipoxygenase and consequent accumulation of 15(S)-HETE ethanolamine may contribute to decreased visual function in glaucomatous mice. Since N-acylethanolamines effectively attenuate glaucoma pathogenesis and associated visual impairment, our data provides additional rationale and novel targets for glaucoma therapies.
authors.affiliation: Department of Ophthalmology, Vision Research Center, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
authors.forename: Christa L
authors.initials: CL
authors.lastname: Montgomery
authors.affiliation: Department of Biological Sciences, Center for Plant Lipid Research, University of North Texas, Denton, TX, USA.
authors.forename: Jantana
authors.initials: J
authors.lastname: Keereetaweep
authors.affiliation: Department of Ophthalmology, Vision Research Center, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Johnson
authors.affiliation: Department of Ophthalmology, Vision Research Center, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Grillo
authors.affiliation: Department of Biological Sciences, Center for Plant Lipid Research, University of North Texas, Denton, TX, USA.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Chapman
authors.affiliation: Department of Ophthalmology, Vision Research Center, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, 64108, USA. koulenp@umkc.edu.|Department of Biological Sciences, Center for Plant Lipid Research, University of North Texas, Denton, TX, USA. koulenp@umkc.edu.|Department of Basic Medical Science, School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA. koulenp@umkc.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Koulen
mesh_terms: D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D004983:Ethanolamines / Q000032:analysis* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005901:Glaucoma / Q000378:metabolism / Q000503:physiopathology*; D007429:Intraocular Pressure; D051379:Mice; D054883:Oxylipins / Q000032:analysis* / Q000378:metabolism; D012160:Retina / Q000378:metabolism / Q000503:physiopathology*; D014792:Visual Acuity
chemical_list: D004983:Ethanolamines; C022203:N-acylethanolamines; D054883:Oxylipins
keywords: Acylethanolamides; Anandamide; Contrast sensitivity; DBA/2; Intraocular pressure; Lipoxin; Lipoxygenase; N-Linoleoylethanolamine; N-Oleylethanolamine; Neuroprotection; Optokinetic reflex; Optomotor; Visual acuity