Changes in Retinal N-Acylethanolamines and their Oxylipin Derivatives During the Development of Visual Impairment in a Mouse Model for Glaucoma

卷:51

Montgomery, Christa L. ; Keereetaweep, Jantana ; Johnson, Heather M. ; Grillo, Stephanie L. ; Chapman, Kent D. ; Koulen, Peter

Univ Missouri

关键词: Acylethanolamides;    Anandamide;    Contrast sensitivity;    DBA/2;    Intraocular pressure;    Lipoxin;    Lipoxygenase;    Neuroprotection;    N-Linoleoylethanolamine;    N-Oleylethanolamine;    Optokinetic reflex;    Optomotor;    Visual acuity;   

DOI  :  10.1007/s11745-016-4161-x

学科分类：食品科学和技术

【 摘 要 】

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.