Lynda A Wilmott1, Richard C Grambergs1, Jeremy C Allegood2, Timothy J Lyons3, Nawajes Mandal4. 1. The University of Tennessee Health Science Center, Department of Ophthalmology, Memphis, TN 38163, USA. 2. Virginia Commonwealth University School of Medicine, Lipidomics Core, Department of Biochemistry and Molecular Biology, Richmond, VA 23298, USA. 3. Medical University of South Carolina, Division of Endocrinology, Diabetes & Medical Genetics, Charleston, SC 29425, USA. 4. The University of Tennessee Health Science Center, Department of Ophthalmology, Memphis, TN 38163, USA; The University of Tennessee Health Science Center, Department of Anatomy and Neurobiology, Memphis, TN 38163, USA; The University of Oklahoma Health Science Center, Department of Ophthalmology, Oklahoma City, OK 73104, USA. Electronic address: nmandal@uthsc.edu.
Abstract
OBJECTIVE: Sphingolipids have a fundamental role in many cellular processes, and they have been implicated in insulin resistance and Diabetes Mellitus (DM) and its complications, including diabetic retinopathy (DR). Little is known about how bioactive sphingolipids relate to retinopathies in human DM. In this study, we analyzed the sphingolipid composition of type 2 diabetic (T2DM) and non-diabetic human vitreous samples. METHODS: We conducted an observational study on post-mortem human vitreous samples from non-diabetic (Controls; n = 4; age: 71.6 ± 11.0 years, mean ± SD) and type 2 diabetic (T2DM; n = 9; age: 67.0 ± 9.2 years) donors to identify changes in sphingolipid composition. Samples were analyzed by a triple quadrupole mass spectrometer and individual sphingolipid species were identified and quantified using established protocols. RESULTS: The total quantity (pmol/mg) of ceramide (Cer), lactosylceramide (Lac-Cer), and sphingomyelin (SM) were increased in type 2 diabetic vitreous samples. Among individual species, we found a general trend of increase in the longer chain species of ceramides, hexosylceramides (Hex-Cer), Lac-Cer, and SM. CONCLUSIONS: This study shows the presence of measurable levels of sphingolipids in human vitreous. The results indicate changes in sphingolipid composition in the vitreous due to type 2 diabetes, which could be connected to the disease pathologies of the retina, retinal vessels, vitreous and the surrounding tissues.
OBJECTIVE:Sphingolipids have a fundamental role in many cellular processes, and they have been implicated in insulin resistance and Diabetes Mellitus (DM) and its complications, including diabetic retinopathy (DR). Little is known about how bioactive sphingolipids relate to retinopathies in humanDM. In this study, we analyzed the sphingolipid composition of type 2 diabetic (T2DM) and non-diabetichuman vitreous samples. METHODS: We conducted an observational study on post-mortem human vitreous samples from non-diabetic (Controls; n = 4; age: 71.6 ± 11.0 years, mean ± SD) and type 2 diabetic (T2DM; n = 9; age: 67.0 ± 9.2 years) donors to identify changes in sphingolipid composition. Samples were analyzed by a triple quadrupole mass spectrometer and individual sphingolipid species were identified and quantified using established protocols. RESULTS: The total quantity (pmol/mg) of ceramide (Cer), lactosylceramide (Lac-Cer), and sphingomyelin (SM) were increased in type 2 diabetic vitreous samples. Among individual species, we found a general trend of increase in the longer chain species of ceramides, hexosylceramides (Hex-Cer), Lac-Cer, and SM. CONCLUSIONS: This study shows the presence of measurable levels of sphingolipids in human vitreous. The results indicate changes in sphingolipid composition in the vitreous due to type 2 diabetes, which could be connected to the disease pathologies of the retina, retinal vessels, vitreous and the surrounding tissues.
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