Daytime Lipid Metabolism Modulated by <i>CLOCK</i> Gene Is Linked to Retinal Ganglion Cells Damage in Glaucoma
Lipid metabolism is intimately linked to circadian mechanisms and light signaling. Deteriorated photic transduction because of retinal ganglion cell (RGC) loss occurring with glaucoma progression reduces perceived light amplitude, causing circadian disruption. To investigate associations with RGCs,...
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MDPI AG
2022-06-01
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| Online Access: | https://www.mdpi.com/2076-3417/12/13/6374 |
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| author | Denis Gubin Vladimir Neroev Tatyana Malishevskaya Sergey Kolomeichuk Dietmar Weinert Natalya Yuzhakova Alsu Nelaeva Yulia Filippova Germaine Cornelissen |
| author_facet | Denis Gubin Vladimir Neroev Tatyana Malishevskaya Sergey Kolomeichuk Dietmar Weinert Natalya Yuzhakova Alsu Nelaeva Yulia Filippova Germaine Cornelissen |
| author_sort | Denis Gubin |
| collection | DOAJ |
| description | Lipid metabolism is intimately linked to circadian mechanisms and light signaling. Deteriorated photic transduction because of retinal ganglion cell (RGC) loss occurring with glaucoma progression reduces perceived light amplitude, causing circadian disruption. To investigate associations with RGCs, total cholesterol (TC), its low-density (LDL-C) and high-density (HDL-C) fractions, and triglycerides (TG) were measured, under a controlled meal regimen, during daytime hours in 114 patients diagnosed with primary open-angle glaucoma (POAG). RGC damage was assessed by high-definition optical coherence tomography (HD-OCT). Analysis of eight clock, clock-related, and melatonin receptor gene polymorphisms was performed on 19 patients. RGC loss was associated with changes in lipid metabolism in a time-dependent manner. Morning (08:00) values of HDL-C (r = 0.613, <i>p</i> < 0.0001) and TG (r = 0.568, <i>p</i> < 0.0001) correlated positively with RGC global loss, while LDL-C at 08:00 had a weak correlation (r = 0.235; <i>p</i> = 0.012) but showed a strong correlation in the evening (20:00) (r = 0.533, <i>p</i> < 0.0001). The morning–evening gradients (MEGs, changes at 20:00 versus 08:00) in TC and LDL-C changed sign from a negative to a positive association in patients exceeding the 15% two-eye mean GLV threshold. MEG (LDL-C higher in the evening than in the morning) was positive only in POAG patients with the CLOCK_3111 TT genotype. |
| first_indexed | 2024-03-09T22:09:07Z |
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| issn | 2076-3417 |
| language | English |
| last_indexed | 2024-03-09T22:09:07Z |
| publishDate | 2022-06-01 |
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| series | Applied Sciences |
| spelling | doaj.art-241fd36b4ddb45f8a10ff5cfbe6b10862023-11-23T19:35:36ZengMDPI AGApplied Sciences2076-34172022-06-011213637410.3390/app12136374Daytime Lipid Metabolism Modulated by <i>CLOCK</i> Gene Is Linked to Retinal Ganglion Cells Damage in GlaucomaDenis Gubin0Vladimir Neroev1Tatyana Malishevskaya2Sergey Kolomeichuk3Dietmar Weinert4Natalya Yuzhakova5Alsu Nelaeva6Yulia Filippova7Germaine Cornelissen8Laboratory for Chronobiology and Chronomedicine, Research Institute of Biomedicine and Biomedical Technologies, Medical University, 625023 Tyumen, RussiaHelmholtz Research Institute of Eye Diseases, 105062 Moscow, RussiaHelmholtz Research Institute of Eye Diseases, 105062 Moscow, RussiaLaboratory for Genomics, Metabolomics and Proteomics, Research Institute of Biomedicine and Biomedical Technologies, Medical University, 625023 Tyumen, RussiaDepartment of Zoology, Institute of Biology/Zoology, Martin Luther University, 06108 Halle, GermanyLaboratory for Genomics, Metabolomics and Proteomics, Research Institute of Biomedicine and Biomedical Technologies, Medical University, 625023 Tyumen, RussiaDepartment of Endocrinology, Medical University, 625023 Tyumen, RussiaState Autonomous Health Care Institution Tyumen Regional Ophthalmological Dispensary, 625048 Tyumen, RussiaHalberg Chronobiology Center, University of Minnesota, Minneapolis, MN 55455, USALipid metabolism is intimately linked to circadian mechanisms and light signaling. Deteriorated photic transduction because of retinal ganglion cell (RGC) loss occurring with glaucoma progression reduces perceived light amplitude, causing circadian disruption. To investigate associations with RGCs, total cholesterol (TC), its low-density (LDL-C) and high-density (HDL-C) fractions, and triglycerides (TG) were measured, under a controlled meal regimen, during daytime hours in 114 patients diagnosed with primary open-angle glaucoma (POAG). RGC damage was assessed by high-definition optical coherence tomography (HD-OCT). Analysis of eight clock, clock-related, and melatonin receptor gene polymorphisms was performed on 19 patients. RGC loss was associated with changes in lipid metabolism in a time-dependent manner. Morning (08:00) values of HDL-C (r = 0.613, <i>p</i> < 0.0001) and TG (r = 0.568, <i>p</i> < 0.0001) correlated positively with RGC global loss, while LDL-C at 08:00 had a weak correlation (r = 0.235; <i>p</i> = 0.012) but showed a strong correlation in the evening (20:00) (r = 0.533, <i>p</i> < 0.0001). The morning–evening gradients (MEGs, changes at 20:00 versus 08:00) in TC and LDL-C changed sign from a negative to a positive association in patients exceeding the 15% two-eye mean GLV threshold. MEG (LDL-C higher in the evening than in the morning) was positive only in POAG patients with the CLOCK_3111 TT genotype.https://www.mdpi.com/2076-3417/12/13/6374glaucomaretinal ganglion cellsmetabolismlipidscholesteroltriglycerides |
| spellingShingle | Denis Gubin Vladimir Neroev Tatyana Malishevskaya Sergey Kolomeichuk Dietmar Weinert Natalya Yuzhakova Alsu Nelaeva Yulia Filippova Germaine Cornelissen Daytime Lipid Metabolism Modulated by <i>CLOCK</i> Gene Is Linked to Retinal Ganglion Cells Damage in Glaucoma Applied Sciences glaucoma retinal ganglion cells metabolism lipids cholesterol triglycerides |
| title | Daytime Lipid Metabolism Modulated by <i>CLOCK</i> Gene Is Linked to Retinal Ganglion Cells Damage in Glaucoma |
| title_full | Daytime Lipid Metabolism Modulated by <i>CLOCK</i> Gene Is Linked to Retinal Ganglion Cells Damage in Glaucoma |
| title_fullStr | Daytime Lipid Metabolism Modulated by <i>CLOCK</i> Gene Is Linked to Retinal Ganglion Cells Damage in Glaucoma |
| title_full_unstemmed | Daytime Lipid Metabolism Modulated by <i>CLOCK</i> Gene Is Linked to Retinal Ganglion Cells Damage in Glaucoma |
| title_short | Daytime Lipid Metabolism Modulated by <i>CLOCK</i> Gene Is Linked to Retinal Ganglion Cells Damage in Glaucoma |
| title_sort | daytime lipid metabolism modulated by i clock i gene is linked to retinal ganglion cells damage in glaucoma |
| topic | glaucoma retinal ganglion cells metabolism lipids cholesterol triglycerides |
| url | https://www.mdpi.com/2076-3417/12/13/6374 |
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