Spatial organization of lipids in the human retina and optic nerve by MALDI imaging mass spectrometry

Abstract

This article is available online at http://www.jlr.org signals to the visual centers of the brain ( 1 ). The central region is made up of several layers that include the horizontal, bipolar, and amacrine cells, which collectively process visual information from the photoreceptors, transmitting these signals to the ganglion cells. The outermost retinal neurons, the photoreceptors, are responsible for phototransduction ( 2 ). There are two types of photoreceptors, which include rods that are present in the peripheral retina and cones that are present in the central (macular) region of the retina. Rods function in dim light and manage peripheral and night vision, whereas cones are responsible for central high acuity bright light vision. The outermost layer of the retina, the retinal pigment epithelium (RPE), serves many functions, including the isomerization of all-trans retin ol into 11-cis retin al in the visual cycle, phagocytosis and degradation of shed photoreceptor tips, and the phagocytic clearance of cellular debris resulting from apoptotic and necrotic processes ( 3 ).The lipids present in the retina are highly unique and play a critical role in retina function and disease. The retina is a tissue that is highly enriched in PUFAs with DHA (22:6) (22 carbons with 6 double bonds) accounting for approximately 50% of the fatty acids in the photoreceptors ( 4 ). This large amount of DHA results in a highly fl uid membrane that permits effi cient conformational changes to occur in rhodopsin and its associated G-protein during phototransduction ( 5 ). Moreover, DHA is converted into neuroprotectin D1, a potent mediator that evokes counteracting cell-protective anti-infl ammatory pro-survival repair signaling, including the induction of anti-apoptotic proteins and inhibition of pro-apoptotic proteins, activating signaling pathway(s) that modulate(s) pro-apoptotic Abstract MALDI imaging mass spectrometry (IMS) was used to characterize lipid species within sections of human eyes. Common phospholipids that are abundant in most tissues were not highly localized and observed throughout the accessory tissue, optic nerve, and retina. Triacylglycerols were highly localized in accessory tissue, whereas sulfatide and plasmalogen glycerophosphoethanolamine (PE) lipids with a monounsaturated fatty acid were found enriched in the optic nerve. Additionally, several lipids were associated solely with the inner retina, photoreceptors, or retinal pigment epithelium (RPE); a plasmalogen PE lipid containing DHA ( The retina is a light-sensitive multi-layered tissue that lines the back of the eye and is responsible for converting light into a neural signal. The innermost layer of the retina, which is closest to the lens, contains ganglion cells that are the output neurons which comprise the optic nerve and conduct

Eicosanoid storm in infection and inflammation

“…Hopefully, future developments in lipidomics such as secondary ion mass spectrometry (SIMS-C 60 ), which allows for profiling of lipids at the single-cell level 71 , may provide a useful platform to eventually solve the current debate over the presence of and biological relevancies of specific eicosanoids in specific cells during infection and inflammation. Recent studies on the spatial organization of lipids in the human retina and optic nerve by matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry 72 identified individual phospholipids, some containing DHA, in different layers of the human retina, suggesting that with future technological advances local pools of released fatty acids and eicosanoid products may be detectable in relevant human tissues under inflammatory conditions.…”

A MALDI-MSI Approach to the Characterization of Radiation-Induced Lung Injury and Medical Countermeasure Development

“…This molecular imaging technique has been applied to the investigation of lipids, metabolites and proteins in a plethora of pathophysiological processes(Carter et al 2011, Palmer et al 2012, Steven and Bunch 2013, Berry et al 2014, Djidja et al 2014, Jackson et al 2014, Jones et al 2014, Manier et al 2014, Seeley et al 2014, Shariatgorji et al 2014). By applying mass spectrometry to region-specific anatomical tissue architecture, MALDI-MSI offers another dimension in characterizing the natural history and development of these pathologies.…”

“…There is currently limited information on the spatial distribution of biologically active small molecules in the lung in a physiological state(Sparvero et al 2012, Berry et al 2014) and in the numerous pathologies that present following radiation insult, and the devastating pneumonitis and fibrosis that develop. Work presented in this study documents lipidomic distribution and dysregulation in the lung following whole-thorax lung irradiation, as well as the detection and localization of AEOL 10150 within the lung tissue following irradiation and treatment.…”

High Spatial Resolution Imaging Mass Spectrometry of Human Optic Nerve Lipids and Proteins

“…The method is particularly well-suited for examining tissues of the eye as demonstrated by published images of lens [12–18], retina [19–24], and optic nerve [21, 25] tissues. In recent reports, distinct cell layers of the retina have been distinguished by IMS where unique lipid and metabolite signatures appear for each retinal layer [19, 21]. In optic nerve imaging studies, distinct lipid signatures have been reported for nerve fiber layers and surrounding dura mater in images acquired from rodent optic nerve tissue [25].…”