Effects of Dyslipidemia in Diet-Induced Obesity and Aging on the Meibomian Gland and Ocular Surface

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dc.contributor.advisorBurns, Alan R.
dc.contributor.committeeMemberRedfern, Rachel
dc.contributor.committeeMemberRumbaut, Rolando E.
dc.contributor.committeeMemberSteven, Philipp
dc.creatorOsae, Eugene A
dc.creator.orcid0000-0002-2059-7823
dc.date.accessioned2022-06-18T23:36:40Z
dc.date.createdAugust 2021
dc.date.issued2021-08
dc.date.submittedAugust 2021
dc.date.updated2022-06-18T23:36:41Z
dc.description.abstractPurpose: Using a mouse model of diet-induced obesity where dyslipidemia is present, this dissertation evaluates the hypothesis that dyslipidemia alters meibum composition which in turn impacts the tear film, meibomian gland and ocular surface morphology. The first aim determines if alterations in plasma (systemic) lipids during dyslipidemia are mirrored by changes in meibum lipids and tear production using a diet-induced mouse model of obesity. The second aim determines if meibomian glands and the ocular surface morphology change during dyslipidemia and the third aim determines if dyslipidemia is associated with changes in meibum-synthesizing peroxisomes. Methods: 5-week-old male C57/BL6 mice were fed a normal (ND; 15% kcal fat) or an obesogenic high-fat diet (HFD; 42% kcal milk fat) for 10 weeks. Body weight and adiposity (epidydimal adipose tissue weight) were recorded. Plasma and meibum samples were obtained for targeted lipidomic analysis of cholesteryl esters (CE), triglycerides (TG), ceramides (Cer) and sphingomyelins (SM) using Nano-ESI-MS/MS and LC-ESI-MS/MS. Eyelids were harvested for meibomian gland morphological analysis and corneas obtained for scanning electron evaluation of ocular surface microplicae. Aged mice were also included for comparison. Meibocyte peroxisomes were evaluated by transcriptomic and immunohistochemical analysis of peroxisomal PEX 14, ABCD1, ABCD3 and ACOX1. Results: HFD mice gained ≈ 30% more weight and showed significant dyslipidemia with ≈ 2-3-fold increase in plasma CE, TG, and SM than ND mice. Increased body weight correlated with plasma CE, TG and SM, p<0.01-<0.0001. HFD mice also showed increased saturation in most meibum lipid species. The change in plasma TGs mirrored meibum TGs. Alterations in meibum were accompanied by excessive (2-fold more) aqueous tear production and ≈ 25% larger meibomian gland area and reductions in corneal epithelial microplicae coverage. Aging was associated with a downregulation (≈2-4) in peroxisomal enzymes PEX14, ABCD1 and ABCD3 in the presence of dyslipidemia. Conclusions: Dyslipidemia (diet-induced or age-induced) is linked to MGD. The increased saturation of meibum and the associated excessive aqueous tear production as well as re-organization of ocular surface (corneal) epithelial microplicae are consistent with MGD and dry eye. Controlling the plasma lipid profile may be an effective strategy for managing MGD patients.
dc.description.departmentOptometry, College of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.citationPortions of this document appear in: Osae EA, Steven P, Redfern R, Hanlon S, Smith CW, Rumbaut RE, Burns AR. Dyslipidemia and Meibomian Gland Dysfunction: Utility of Lipidomics and Experimental Prospects with a Diet-Induced Obesity Mouse Model. International Journal of Molecular Sciences. 2019; 20(14):3505; and in: Osae EA, Bullock T, Chintapalati M, Brodesser S, Hanlon S, Redfern R, Steven P, Smith CW, Rumbaut RE, Burns AR. Obese Mice with Dyslipidemia Exhibit Meibomian Gland Hypertrophy and Alterations in Meibum Composition and Aqueous Tear Production. International Journal of Molecular Sciences. 2020; 21(22):8772
dc.identifier.urihttps://hdl.handle.net/10657/9382
dc.language.isoeng
dc.rightsThe author of this work is the copyright owner. UH Libraries and the Texas Digital Library have their permission to store and provide access to this work. UH Libraries has secured permission to reproduce any and all previously published materials contained in the work. Further transmission, reproduction, or presentation of this work is prohibited except with permission of the author(s).
dc.subjectObesity
dc.subjectDyslipidemia
dc.subjectMeibomian glands
dc.subjectOcular surface
dc.subjectDry eye
dc.subjectMeibum
dc.subjectTear film
dc.subjectPeroxisome
dc.subjectLipids
dc.titleEffects of Dyslipidemia in Diet-Induced Obesity and Aging on the Meibomian Gland and Ocular Surface
dc.type.dcmiText
dc.type.genreThesis
dcterms.accessRightsThe full text of this item is not available at this time because the student has placed this item under an embargo for a period of time. The Libraries are not authorized to provide a copy of this work during the embargo period.
local.embargo.lift2023-08-01
local.embargo.terms2023-08-01
thesis.degree.collegeCollege of Optometry
thesis.degree.departmentOptometry, College of
thesis.degree.disciplinePhysiological Optics and Vision Science
thesis.degree.grantorUniversity of Houston
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

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