Human Trabecular Meshwork Sphingolipid and Ceramide Profiles and Potential Latent Fungal Commensalism

Aljohani, Ayman; Edwards, Genea; Guerra, Yenifer; Dubovy, Sander R.; Miller, Darlene; Lee, Richard K.; Bhattacharya, Sanjoy K.

doi:10.1167/iovs.13-13570

Cited by 14 publications

(13 citation statements)

References 51 publications

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“…Samples were injected as direct infusion using a Triversa Nanomate driven by Chipsoft 8.3 (Advion Inc). The samples were run with and without addition of lipid standards for each class of lipids analysed as done in our previous studies . In addition, an unrelated lipid standard was used during extraction.…”

Section: Methodsmentioning

confidence: 99%

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Endogenous ocular lipids as potential modulators of intraocular pressure

Edwards

Arcuri

Wang

et al. 2020

J Cellular Molecular Medi

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Elevated intraocular pressure (IOP) is a risk factor in glaucoma, a group of irreversible blinding diseases. Endogenous lipids may be involved in regulation of IOP homeostasis. We present comparative fold analysis of phospholipids and sphingolipids of aqueous humour and trabecular meshwork from human control vs primary openangle glaucoma and mouse control (normotensive) vs ocular hypertensive state. The fold analysis in control vs disease state was based on ratiometric mass spectrometric data for above classes of lipids. We standardized in vitro assays for rapid characterization of lipids undergoing significant diminishment in disease state. Evaluation of lipids using in vitro assays helped select a finite number of lipids that may potentially expand cellular interstitial space embedded in an artificial matrix or increase fluid flow across a layer of cells. These assays reduced a number of lipids for initial evaluation using a mouse model, DBA/2J with spontaneous IOP elevation. These lipids were then used in other mouse models for confirmation of IOP lowering potential of a few lipids that were found promising in previous assessments. Our results provide selected lipid molecules that can be pursued for further evaluation and studies that may provide insight into their function. K E Y W O R D Saqueous humour, glaucoma, lipidomics, lipids, trabecular meshwork | 3857 EDWARDS Et Al.

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Section: Methodsmentioning

confidence: 99%

“…Normal AH has been shown to contain diverse phospholipids (PLs) . The TM and AH phospholipids and sphingolipids of human control and POAG as well as normotensive and ocular hypertensive DBA/2J mouse have been previously analysed using moderate‐resolution mass spectrometers …”

Section: Introductionmentioning

confidence: 99%

Endogenous ocular lipids as potential modulators of intraocular pressure

Edwards

Arcuri

Wang

et al. 2020

J Cellular Molecular Medi

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“…The sphingolipid base analog, iso (4E,15-methyl-d16:1) sphingosine is likely involved in cell survival, cell growth and proliferation and related physiological processes [56], C16 sphinganine Sphinganine-1-phosphate level changes has been noted with fumonisin B 1 toxicity [57]. Fumonisins are fungal lipids that may occur in the anterior eye tissue either from local infection/commensalism or assimilated from contaminated food [58]. They structurally mimic sphingoid bases and act as competitive inhibitors of sphingolipid biosynthesis and metabolism [58-61].…”

Section: Discussionmentioning

confidence: 99%

“…Fumonisins are fungal lipids that may occur in the anterior eye tissue either from local infection/commensalism or assimilated from contaminated food [58]. They structurally mimic sphingoid bases and act as competitive inhibitors of sphingolipid biosynthesis and metabolism [58-61]. PhS1P has been recently implicated in cellular stress responses in yeast [62], and also act as a high affinity ligand for the S1P 4 receptors [63] and may potentially be involved in cell signaling [64, 65].…”

Section: Discussionmentioning

confidence: 99%

Sphingolipids and ceramides of mouse aqueous humor: Comparative profiles from normotensive and hypertensive DBA/2J mice

et al. 2014

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Purpose To identify the sphingolipid and ceramide species and their quantitative differences between normotensive and hypertensive intraocular pressure states in DBA/2J mouse aqueous humor (AH). Methods Normotensive and hypertensive AH was sampled from mice by paracentesis. Lipid extraction was performed using modifications of the Bligh and Dyer method. Protein concentration was estimated using the Bradford colorimetric assay. Sphingolipids and ceramides were identified and subjected to ratiometric quantification using appropriate class specific lipid standards on a TSQ Quantum Access Max triple quadrupole mass spectrometer. Results The comparative profiles of normotensive and hypertensive DBA/2J mouse AH showed several species of sphingomyelin, sphingoid base, sphingoid base-1-phosphate (S1P) and ceramides common between them. A number of unique lipids in each of the above lipid classes were also identified in normotensive AH that were absent in hypertensive AH and vice versa. Conclusion A number of sphingolipid and ceramide species were found to be uniquely present in normotensive, but absent in hypertensive AH and vice versa. Further pursuit of these findings is likely to contribute towards expanding our understanding of the molecular changes associated with increased intraocular pressure (IOP) and glaucoma.

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“…Among these methods, the main technology is electrospray ionization mass spectrometry, which exhibits high throughput, efficiency and sensitivity. 7 Lipidomics has been applied in a series of studies on several diseases, including infectious diseases, 8,9 cancers, 10 neurological disorders, 11 metabolic diseases, 12 and cardiovascular disorders. 13 Research shows that sphingolipids, cholesteryl esters, glycerolipids and phospholipids (including lyso-and ether-species) have potential as biomarkers for type 2 diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%