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Relationships between ocular surface sphingomyelinases,Meibum and Tear Sphingolipids,and clinical parameters of meibomian gland dysfunction
Institution:1. Miami Veterans Administration Medical Center, 1201 NW 16th St, Miami, FL, 33125, USA;2. New York University Grossman School of Medicine, New York, NY, 10016, USA;3. Bascom Palmer Eye Institute, University of Miami, 900 NW 17th Street, Miami, FL, 33136, USA;4. Department of Ophthalmology, University of Tennessee Health Sciences Center, Hamilton Eye Institute, 930 Madison Avenue, Memphis, TN, 38163, USA;5. Departments of Anatomy and Neurobiology, Pharmaceutical Sciences, University of Tennessee Health Sciences Center, 930 Madison Avenue, Memphis, TN, 38163, USA;6. Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA;1. Rothschild Foundation Hospital, Paris, France;2. Paris University, Paris, France;1. Eye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA;2. Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA;3. Department of Medicine, University of Southern California, Los Angeles, CA, USA;4. David Geffen School of Medicine at UCLA, Los Angeles, CA, USA;1. Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, Auckland, New Zealand;2. Department of Molecular Medicine and Pathology, The University of Auckland, Auckland, New Zealand;3. Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, The University of Auckland, Auckland, New Zealand;4. Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
Abstract:PurposeSphingolipids (SPL) are a class of lipid molecules that play important functional and structural roles in our body and are a component of meibum. Sphingomyelinases (SMases) are key enzymes in sphingolipid metabolism that hydrolyze sphingomyelin (SM) and generate ceramide (Cer). The purpose of this study was to examine relationships between ocular surface SMases, SPL composition, and parameters of Meibomian gland dysfunction (MGD).MethodsIndividuals were grouped by meibum quality (n = 25 with poor-quality, MGD, and n = 25 with good-quality, control). Meibum and tears were analyzed with LC-MS to quantify SPL classes: Cer, Hexosyl-Ceramide (Hex-Cer), SM, Sphingosine (Sph), and sphingosine 1-phosphate (S1P). SMase activity in tears were quantified using a commercially available ‘SMase assay’. Statistical analysis included multiple linear regression analyses to assess the impact of SMase activity on lipid composition, as well as ocular surface symptoms and signs of MGD.ResultsDemographic characteristics were similar between the two groups. nSMase and aSMase levels were lower in the poor vs good quality group. aSMase activity in tears negatively correlated with SM in meibum and tears and positively with Sph in meibum and S1P in tears. Lower SMase activity were associated with signs of MGD, most notably Meibomian gland dropout.ConclusionThis study suggests that individuals with MGD have reduced enzymatic activity of SMases in tears. Specifically, individuals with poor vs good meibum quality were noted to have alterations in SMase activity and SPL composition of meibum and tears which may reflect deviations from normal lipid metabolism in individuals with MGD.
Keywords:Sphingomyelinases  Sphingolipid  Ceramide  Sphingomyelin  Sphingosine 1-phosphate  Meibomian gland dysfunction  Tear film
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