Comparative Phospholipid Profiles of Control and Glaucomatous Human Trabecular Meshwork

Aribindi, Katyayini; Guerra, Yenifer; Lee, Richard K.; Bhattacharya, Sanjoy K.

doi:10.1167/iovs.12-10517

Cited by 32 publications

(66 citation statements)

References 34 publications

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“…Only, very recently, lipidomic analyses have been undertaken to examine the distribution profile of different phospholipids, ceramides, and glycosphingolipids in AH and TM tissue from both normal and glaucomatous eyes by mass spectrometric methods. [115][116][117] Importantly, these emerging analyses have started to unravel the presence of several distinct and common phospholipids, ceramides, and glycosphingolipids in normal and glaucoma specimens. [115][116][117] In addition, the levels of both phospholipids and glycosphingolipids were reported to be decreased in the glaucomatous AH and TM, indicating their potential role in the pathophysiology of glaucoma and elevated IOP.…”

Section: Raomentioning

confidence: 99%

“…[115][116][117] Importantly, these emerging analyses have started to unravel the presence of several distinct and common phospholipids, ceramides, and glycosphingolipids in normal and glaucoma specimens. [115][116][117] In addition, the levels of both phospholipids and glycosphingolipids were reported to be decreased in the glaucomatous AH and TM, indicating their potential role in the pathophysiology of glaucoma and elevated IOP. 115,116 Therefore, an additional and comprehensive lipidomics analysis of various bioactive lipids in glaucoma and normal…”

Section: Raomentioning

confidence: 99%

“…[115][116][117] In addition, the levels of both phospholipids and glycosphingolipids were reported to be decreased in the glaucomatous AH and TM, indicating their potential role in the pathophysiology of glaucoma and elevated IOP. 115,116 Therefore, an additional and comprehensive lipidomics analysis of various bioactive lipids in glaucoma and normal…”

Section: Raomentioning

confidence: 99%

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Bioactive Lysophospholipids: Role in Regulation of Aqueous Humor Outflow and Intraocular Pressure in the Context of Pathobiology and Therapy of Glaucoma

Rao

2014

Journal of Ocular Pharmacology and Therapeutics

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Homeostasis of aqueous humor (AH) outflow and intraocular pressure (IOP) is essential for normal vision. Impaired AH outflow through the trabecular meshwork (TM) and a resultant elevation in IOP are common changes in primary open-angle glaucoma (POAG), which is the most prevalent form of glaucoma. Although elevated IOP has been recognized as a definitive risk factor for POAG and lowering elevated IOP remains a mainstay for glaucoma treatment, little is known about the molecular mechanisms, especially external cues and intracellular pathways, involved in the regulation of AH outflow in both normal and glaucomatous eyes. In addition, despite the recognition that increased resistance to AH outflow via the conventional pathway consisting of TM and Schlemm's canal is the main cause for elevated IOP, there are no clinically approved drugs that target the conventional pathway to lower IOP in glaucoma patients. The aim of this article is to briefly review published work on the importance of bioactive lysophospholipids (eg, lysophosphatidic acid and sphingosine-1-phosphate), their receptors, metabolism, signaling, and role in the regulation of AH outflow via the TM and IOP, and to discuss pharmacological targeting of key proteins in the lysophospholipid signaling pathways to lower IOP in glaucoma patients.

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Section: Raomentioning

confidence: 99%

Section: Raomentioning

confidence: 99%

Section: Raomentioning

confidence: 99%

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Bioactive Lysophospholipids: Role in Regulation of Aqueous Humor Outflow and Intraocular Pressure in the Context of Pathobiology and Therapy of Glaucoma

Rao

2014

Journal of Ocular Pharmacology and Therapeutics

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“…Since at 8, 10, and 12 months, the IOP elevation is asynchronous, 10,13,14 mice at these ages, which did not exceed an IOP of 17 mm of Hg, were excluded from the study. TM tissues were subjected to lipid extraction using suitable modification 15 of the Bligh and Dryer method. 16 All extractions were made without addition of any extraneous ions such as lithium or acetate ions unless stated otherwise.…”

Section: Animal Tissues and Lipid Extractionmentioning

confidence: 99%

“…The corresponding aqueous phase was used for protein quantification 15 using the Bradford method 17 for protein normalized lipid estimation. Uniformity of extraction was ensured with an added external standard (1, 2-ditridecanoyl-snglycero-3-phosphocholine) during tissue homogenization.…”

Section: Animal Tissues and Lipid Extractionmentioning

confidence: 99%

A Comparison of Trabecular Meshwork Sphingolipids and Ceramides of Ocular Normotensive and Hypertensive States of DBA/2J Mice

Guerra

Aljohani

Edwards

et al. 2014

Journal of Ocular Pharmacology and Therapeutics

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Purpose: To determine the differential profiles of sphingomyelin, sphingoid base, sphingoid base-1-phosphate, and ceramide and their quantitative differences between trabecular meshwork (TM) derived from normotensive and hypertensive intraocular pressure states of DBA/2J mice. Methods: Normotensive and hypertensive state TM were collected from mice and analyzed. Lipid extraction was performed using the Bligh and Dyer method, and the protein concentrations were determined using the Bradford method. The lipids were identified and quantified using appropriate standards with a TSQ Quantum Access Max triple quadrupole mass spectrometer applying class-specific lipid identification settings. Results: The comparative profiles of sphingomyelin, sphingoid base, sphingoid base-1-phosphate, and ceramide between normotensive and hypertensive TM showed several species unique to a phase and as well common between states. Conclusion: The presence or absence of several sphingolipids and ceramides in the normotensive or hypertensive states may contribute to better understanding of the glaucomas.

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Phospholipidomic Studies in Human Cornea From Climatic Droplet Keratopathy

Suárez

Piqueras

Correa

et al. 2017

J of Cellular Biochemistry

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Climatic droplet keratopathy (CDK) is an acquired degenerative disease predominantly affecting males over 40 years old. It results in progressive corneal opacities usually affecting both eyes. CDK is multifactorial and its etiology remains unknown. Our recent findings are consistent with CDK pathology being driven by environmental factors with oxidative stress playing an important role (for example, contributing to lipid peroxidation) rather than climate factors. The changes in corneal lipid composition affected by environmental factors remain understudied. The purpose of this study was to systematically investigate phospholipids profile [phosphatidylcholine (PC) and phosphatidylserine (PS)] in corneas from CDK patients using tandem mass spectrometry. Samples from CDK areas and from non-affected areas were obtained from patients diagnosed with CDK who underwent cataract surgery, were subjected to lipid extraction using a modified Bligh and Dyer method; protein concentrations were determined using the Bradford’s method. Lipids were identified and subjected to ratiometric quantification using TSQ Quantum Access Max triple quadrupole mass spectrometer, using appropriate class specific lipid standards. All phospholipid classes showed lower total amounts in affected areas compared to control areas from CDK’s corneas. Comparative profiles of two phospholipid classes (PC, PS) between CDK areas and control areas showed several common species between them. We also found a few unique lipids that were absent in CDK areas compared to controls and vice versa. Lower amount of phospholipids in CDK areas compared to control areas could be attributed to the lipid peroxidation in the affected corneal regions as a consequence of increased oxidative stress.

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Comparative Phospholipid Profiles of Control and Glaucomatous Human Trabecular Meshwork

Abstract: A number of phospholipids were found to be uniquely present in control but absent in glaucomatous TM and vice versa. Compared to a previous study of control and POAG blood, a number of these phospholipids are absent locally (TM), as well as systemically (in blood).

Cited by 32 publications

References 34 publications

Bioactive Lysophospholipids: Role in Regulation of Aqueous Humor Outflow and Intraocular Pressure in the Context of Pathobiology and Therapy of Glaucoma

Bioactive Lysophospholipids: Role in Regulation of Aqueous Humor Outflow and Intraocular Pressure in the Context of Pathobiology and Therapy of Glaucoma

A Comparison of Trabecular Meshwork Sphingolipids and Ceramides of Ocular Normotensive and Hypertensive States of DBA/2J Mice

Phospholipidomic Studies in Human Cornea From Climatic Droplet Keratopathy

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