Diet-Based Strategies for Mitigating Obesity-Induced Corneal Dysregulation: Timing of Diet Intake vs. Macronutrient Composition of Diet

dc.contributor.advisorBurns, Alan R.
dc.contributor.committeeMemberRedfern, Rachel
dc.contributor.committeeMemberHarrison, Wendy W.
dc.contributor.committeeMemberRumbaut, Rolando E.
dc.creatorAkowuah, Prince Kwaku
dc.date.accessioned2023-05-31T17:45:40Z
dc.date.createdDecember 2022
dc.date.issued2022-12-15
dc.date.updated2023-05-31T17:45:41Z
dc.description.abstractPurpose: Diet-induced obesity in mice causes corneal nerve sensitivity and density loss. It also impairs corneal wound healing. Time-restricted feeding and diet reversal are diet-based strategies that target the timing of diet intake and the macronutrient composition of diet, respectively. Although these strategies mitigate cardiometabolic complications of diet-induced obesity, their utility against corneal complications in diet-induced obesity is unknown. Here, a diet-induced obesity mouse model was used to examine the impact of diet's timing and macronutrient composition on obesity-induced corneal dysregulation. Methods: 6-week-old C57BL/6 male mice were used. For the time-restricted feeding experiment, mice were fed either a normal chow diet ad libitum, high-fat/sucrose diet ad libitum (diet-induced obesity), or high-fat/sucrose diet on a time-restricted regimen (8h feed/16h fast period) for 10 days. For the diet reversal experiment, mice were fed either a normal chow diet ad libitum or high-fat/sucrose diet ad libitum for 20 weeks or a high-fat/sucrose diet for 10 weeks and then reversed to a normal chow diet for an additional 10 weeks (diet reversal group). Corneal nerve sensitivity was assessed with a Cochet-Bonnet aesthesiometer. A 2-mm diameter corneal epithelial abrasion wound was created, and wound closure was monitored using sodium fluorescein staining. Neutrophil and platelet recruitment was assessed by immunofluorescence microscopy. Results: Corneal nerve sensitivity was reduced, corneal wound healing was impaired, and inflammation was dysregulated in ad libitum high-fat/sucrose diet-fed mice compared to ad libitum normal diet-fed mice. Time-restricted feeding did not attenuate corneal dysregulation. Corneal nerve sensitivity was reduced, wound closure was delayed, and platelet extravasation at the limbus and neutrophil migration to the center of the cornea were impaired in time-restricted high-fat/sucrose diet-fed mice, similar to that observed in ad libitum high-fat/sucrose diet-fed mice. Diet reversal halted the progression of corneal nerve sensitivity loss, restored normal wound closure and neutrophil and platelet influx in the injured cornea. Conclusion: These data show the cornea is highly responsive to the diet’s macronutrient composition, suggesting compositional changes to the diet may be an effective diet-based therapeutic strategy for maintaining or restoring corneal health.
dc.description.departmentOptometry, College of
dc.format.digitalOriginborn digital
dc.format.mimetypeapplication/pdf
dc.identifier.citationPortions of this document appear in: Akowuah, Prince K., Angie De La Cruz, C. Wayne Smith, Rolando E. Rumbaut, and Alan R. Burns. "An Epithelial Abrasion Model for Studying Corneal Wound Healing." Journal of visualized experiments: JoVE 178 (2021); and in: Akowuah, Prince K., Aubrey Hargrave, Rolando E. Rumbaut, and Alan R. Burns. "Dissociation between Corneal and Cardiometabolic Changes in Response to a Time-Restricted Feeding of a High Fat Diet." Nutrients 14, no. 1 (2021): 139.
dc.identifier.urihttps://hdl.handle.net/10657/14374
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.subjectCornea
dc.subjectWound healing
dc.subjectNerves
dc.titleDiet-Based Strategies for Mitigating Obesity-Induced Corneal Dysregulation: Timing of Diet Intake vs. Macronutrient Composition of Diet
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.lift2024-12-01
local.embargo.terms2024-12-01
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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