Very long-chain fatty acids support synaptic structureand function in the mammalian retina

Oilseeds and fats, crops and lipids

Brush Richard S.¹  Anderson Robert E.¹  Thoreson Wallace B.¹  Van Hook Matthew J.²  Bennett Lea D.³ 

[1] ;Department of Ophthalmology and Visual Sciences, University ofNebraska Medical Center;Retina Foundation of the Southwest;

关键词: ELOVL4;    very long chain fatty acids;    very long chain polyunsaturated fatty acids;    Stargardt-like macular dystrophy;    Lipids in retinal structure and function;   

DOI  :  10.1051/ocl/2015056

来源: DOAJ

【 摘 要 】

Elongation of Very Long chain fatty acids-like 4 (ELOVL4) is a fatty acid elongase responsible for the biosynthesis of very long chain (VLC; ≥ C26) fatty acids in the retina, brain, skin, Meibomian gland, and testes. Heterozygous inheritance of mutant ELOVL4 causes juvenile macular degeneration in autosomal dominant Stargardt-like macular dystrophy (STGD3). Retinal photoreceptors are enriched with VLC polyunsaturated fatty acids (VLC-PUFAs), which have been shown by our group and others to be necessary for the survival of rod photoreceptors. Our group performed a series of studies using mice conditionally depleted of retinal Elovl4 (KO) aimed at understanding the role of VLC-PUFAs in long-term retinal health and function, focusing on the role of these fatty acids in mediating synaptic function between the photoreceptors and the rest of the neural retina. The absence of VLC-PUFA from the retina of KO mice resulted in a marked decrease in retinal b-wave responses of the electroretinogram as well as a decrease in the amplitude of the oscillatory potentials mediated by the neural retina. Although there were no measureable differences between KO and wild type (WT) mice in either pre-synaptic rod calcium channel function or post-synaptic bipolar cell glutamate receptor responses, ultrastructural analysis revealed a marked decrease in the diameter of synaptic vesicles in rod terminals. Recent quantification suggests that this decrease in synaptic vesicle size due to the absence of VLC-PUFAs in KO mice, and the consequent decrease in glutamate content, could account for the decrease in b-wave response amplitudes that were previously measured in these animals.

【 授权许可】

Unknown