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Meibum sphingolipid composition is altered in individuals with meibomian gland dysfunction-a side by side comparison of Meibum and Tear Sphingolipids
Institution:1. Miami Veterans Administration Medical Center, 1201 NW 16th St, Miami, FL, 33125, USA;2. Bascom Palmer Eye Institute, University of Miami, 900 NW 17th Street, Miami, FL, 33136, USA;3. New York University Grossman School of Medicine, New York, NY, 10016, USA;4. Department of Ophthalmology, University of Tennessee Health Sciences Center, Hamilton Eye Institute, 930 Madison Avenue, Memphis, TN, 38163, USA;5. Departments of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, FL, 33620, USA;6. The Moffitt Cancer Center, Tampa, FL, 33620, USA;7. Research Service, James A. Haley Veterans Hospital, Tampa, FL, 33612, USA;8. Departments of Anatomy and Neurobiology, and Pharmaceutical Sciences, University of Tennessee Health Sciences Center, 930 Madison Avenue, Memphis, TN, 38163, USA;9. Memphis VA Medical Center, 1030 Jefferson Avenue, Memphis, TN, 38104, USA;1. Ophthalmic Plastic Surgery Services, L V Prasad Eye Institute, Hyderabad, Telangana, India;2. Centre for Ocular Regeneration, Prof. Brien Holden Centre for Eye Research (BHERC), L V Prasad Eye Institute, Hyderabad, Telangana, India;3. The Cornea Institute, L V Prasad Eye Institute, Hyderabad, Telangana, India;1. University of Cincinnati, Cincinnati, OH, USA;2. Cincinnati Eye Institute, Edgewood, KY, USA;3. Berks Eye Physicians, Wyomissing, Pennsylvania, USA;4. Alberta Retina Consultants, Edmonton, Alberta, Canada;5. Virginia Eye Consultants, Norfolk, VA, USA;1. Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, SeoulSeoul, 03722, Republic of Korea;2. Cornea Dystrophy Research Institute, Department of Ophthalmology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
Abstract:PurposeSphingolipids (SPL) play a role in cell signaling, inflammation, and apoptosis. The purpose of this study was to examine meibum and tear SPL composition in individuals with poor versus good meibum quality.MethodsIndividuals were grouped by meibum quality (n = 25 with poor quality, case group and n = 25 with good quality, control group). Meibum and tears were analyzed with liquid chromatography-mass spectrometry (LC-MS) to quantify SPL classes. Semiquantitative and relative composition (mole percent) of SPL and major classes, Ceramide (Cer), Hexosyl-Ceramide (Hex-Cer), Sphingomyelin (SM), Sphingosine (Sph), and sphingosine 1-phosphate (S1P) were compared between groups.ResultsDemographic characteristics were similar between the two groups. Overall, individuals with poor meibum quality had more SPL pmole in meibum and tears than controls. Relative composition analysis revealed that individuals with poor meibum quality had SPL composed of less Cer, Hex-Cer, and Sph and more SM compared to individuals with good quality meibum. This pattern was not reproduced in tears as individuals with poor meibum quality had SPL composed of a similar amount of Cer, but more Hex-Cer, Sph and SM compared to controls. In meibum, SPL pmole and relative composition most strongly correlated with MG metrics while in tears, SPL pmole and relative composition most strongly correlated with tear production. SPL in both compartments, specifically Cer pmole in meibum and S1P% in tears, correlated with DE symptoms.ConclusionSPL composition differs in meibum and tears in patients with poor vs good meibum quality. These findings may be translated into therapeutic targets for disease.
Keywords:Ceramide  Dry eye  Inflammation  Meibomian gland dysfunction  Sphingolipid  Sphingomyelin  Sphingosine 1-phosphate  Tear film  DE"}  {"#name":"keyword"  "$":{"id":"kwrd0055"}  "$$":[{"#name":"text"  "_":"dry eye  ADDE"}  {"#name":"keyword"  "$":{"id":"kwrd0065"}  "$$":[{"#name":"text"  "_":"aqueous deficient dry eye  EDE"}  {"#name":"keyword"  "$":{"id":"kwrd0075"}  "$$":[{"#name":"text"  "_":"evaporative dry eye  TFLL"}  {"#name":"keyword"  "$":{"id":"kwrd0085"}  "$$":[{"#name":"text"  "_":"tear film lipid layer  MG"}  {"#name":"keyword"  "$":{"id":"kwrd0095"}  "$$":[{"#name":"text"  "_":"meibomian glands  MGD"}  {"#name":"keyword"  "$":{"id":"kwrd0105"}  "$$":[{"#name":"text"  "_":"meibomian glands dysfunction  SPL"}  {"#name":"keyword"  "$":{"id":"kwrd0115"}  "$$":[{"#name":"text"  "_":"Sphingolipids  Cer"}  {"#name":"keyword"  "$":{"id":"kwrd0125"}  "$$":[{"#name":"text"  "_":"ceramide  Sph"}  {"#name":"keyword"  "$":{"id":"kwrd0135"}  "$$":[{"#name":"text"  "_":"sphingosine  C1P"}  {"#name":"keyword"  "$":{"id":"kwrd0145"}  "$$":[{"#name":"text"  "_":"ceramide 1-phosphate  S1P"}  {"#name":"keyword"  "$":{"id":"kwrd0155"}  "$$":[{"#name":"text"  "_":"sphingosine 1-phosphate  Hex-Cer"}  {"#name":"keyword"  "$":{"id":"kwrd0165"}  "$$":[{"#name":"text"  "_":"hexosyl ceramide  SM"}  {"#name":"keyword"  "$":{"id":"kwrd0175"}  "$$":[{"#name":"text"  "_":"sphingomyelin  Sa"}  {"#name":"keyword"  "$":{"id":"kwrd0185"}  "$$":[{"#name":"text"  "_":"sphinganine  SMase"}  {"#name":"keyword"  "$":{"id":"kwrd0195"}  "$$":[{"#name":"text"  "_":"sphingomyelinase  ATD"}  {"#name":"keyword"  "$":{"id":"kwrd0205"}  "$$":[{"#name":"text"  "_":"aqueous tear deficiency  acid sphingomyelinase"}  {"#name":"keyword"  "$":{"id":"kwrd0215"}  "$$":[{"#name":"text"  "_":"aSMase  FFA"}  {"#name":"keyword"  "$":{"id":"kwrd0225"}  "$$":[{"#name":"text"  "_":"free fatty acid  pmole"}  {"#name":"keyword"  "$":{"id":"kwrd0235"}  "$$":[{"#name":"text"  "_":"pico mole
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