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Dietary and Genetic Determinants of ...
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Lawler, Thomas Patrick.
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Dietary and Genetic Determinants of Macular Pigment Density in the Fovea and Relevance for Primary Open-Angle Glaucoma in a Study of Older-Adult Women.
紀錄類型:
書目-電子資源 : Monograph/item
正題名/作者:
Dietary and Genetic Determinants of Macular Pigment Density in the Fovea and Relevance for Primary Open-Angle Glaucoma in a Study of Older-Adult Women./
作者:
Lawler, Thomas Patrick.
出版者:
Ann Arbor : ProQuest Dissertations & Theses, : 2021,
面頁冊數:
251 p.
附註:
Source: Dissertations Abstracts International, Volume: 82-12, Section: B.
Contained By:
Dissertations Abstracts International82-12B.
標題:
Nutrition. -
電子資源:
https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28543484
ISBN:
9798516919817
Dietary and Genetic Determinants of Macular Pigment Density in the Fovea and Relevance for Primary Open-Angle Glaucoma in a Study of Older-Adult Women.
Lawler, Thomas Patrick.
Dietary and Genetic Determinants of Macular Pigment Density in the Fovea and Relevance for Primary Open-Angle Glaucoma in a Study of Older-Adult Women.
- Ann Arbor : ProQuest Dissertations & Theses, 2021 - 251 p.
Source: Dissertations Abstracts International, Volume: 82-12, Section: B.
Thesis (Ph.D.)--The University of Wisconsin - Madison, 2021.
This item must not be sold to any third party vendors.
Part IIn part I of this dissertation, I use data from the Carotenoids in Age-Related Eye Disease Study (CAREDS) to understand factors that positively influence the accumulation of lutein and zeaxanthin (L/Z) as 'macular pigment' in the fovea, with a focus on the use of L/Z supplements, common genetic variants in carotenoid-related candidate genes, and overall diet patterns. In 426 women (age 69-98 years) who attended CAREDS2 follow-up visits (2016-2019), the ad-libitum use of L/Z supplements (≥ 1 mg/day) was associated with larger increases in MPOD over approximately 15 years since baseline (in healthy eyes and eyes with intermediate/advanced macular degeneration) and higher contrast sensitivity (limited to eyes without lens/retinal pathology). Using partial least squares (PLS) regression modeling, I further identified predictor phenotypes and genotypes permissive for the accumulation of macular pigment in women who use L/Z supplements, including greater neural retinal thickness in the fovea. Genetic variants that predict change in MPOD were identified in carotenoid-related candidate genes, including those that facilitate carotenoid absorption (SCARB1 and SCARB2), transport in the bloodstream (LIPC and ABCA1), and binding or metabolism in the retina (STARD3 and RPE65). Dietary recommendations to maximize macular pigment should focus on overall healthy diet patterns (e.g. the heart-healthy Mediterranean Diet pattern), which was associated with higher MPOD in CAREDS through the provision of L/Z in green-leafy vegetables, maintenance of healthy body composition and prevention of metabolic disease. These findings may inform recommendations designed to maximize MPOD in older adults to maintain normal vision for as long as possible, and to mitigate risk for age-related eye disease. Part IIPrimary open-angle glaucoma (POAG) is a common, irreversible neurodegenerative disease of the optic nerve that disproportionately affects older adults. While there are currently few modifiable risk factors for POAG, there is evidence that antioxidants (including L/Z in the retina as macular pigment) may confer protection. In Part II of this dissertation, I used data from the Carotenoids in Age-Related Eye Disease Study (CAREDS) to investigate whether macular pigment density (MPOD), measured at baseline (2001-2004) is associated with manifest primary open-angle glaucoma (POAG) approximately 15 years later in the CAREDS2 follow-up study (2016-2019). In 1258 eyes from participants who completed MPOD testing at CAREDS baseline and adjudication of POAG at CAREDS2, a non-linear protective trend was observed: participants in MPOD quartile 1 (vs. 2-4) were approximately 2x as likely to have POAG at CAREDS2 (p = .07). This association was strengthened in the subgroup of participants with stable MPOD (±0.20 density units) since baseline (p = .01). Notably, an association between MPOD and peripapillary retinal nerve fiber layer (RNFL) thickness (a marker of glaucomatous neurodegeneration in the optic nerve) was not observed. While the nature of this association is not clear, higher MPOD may reflect lifelong adherence to a diet rich in fruits and vegetables, which may have a protective role via mitigation of oxidative stress. In a separate analysis, a single measure of fruit and vegetable consumption at CAREDS baseline was associated with greater peripapillary RNFL thickness at CAREDS2, but was not associated with manifest POAG. We have also observed that higher levels of lutein and zeaxanthin (L/Z) in the retina (as macular pigment) and in the serum are positively associated with the diameter of arterioles and venules in the optic disc, suggesting that L/Z (or healthy diets rich in antioxidants) may be protective in glaucoma by influencing ocular blood flow. While additional longitudinal studies are needed to corroborate the association between MPOD at manifest POAG, our results add to a body of evidence suggesting that antioxidant rich diets containing adequate fruits and vegetables may have a protective role in glaucoma. If confirmed in independent studies, MPOD (which can be measured simply and non-invasively in the clinic) may be useful to identify individuals at elevated risk for POAG.
ISBN: 9798516919817Subjects--Topical Terms:
517777
Nutrition.
Subjects--Index Terms:
Glaucoma
Dietary and Genetic Determinants of Macular Pigment Density in the Fovea and Relevance for Primary Open-Angle Glaucoma in a Study of Older-Adult Women.
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Part IIn part I of this dissertation, I use data from the Carotenoids in Age-Related Eye Disease Study (CAREDS) to understand factors that positively influence the accumulation of lutein and zeaxanthin (L/Z) as 'macular pigment' in the fovea, with a focus on the use of L/Z supplements, common genetic variants in carotenoid-related candidate genes, and overall diet patterns. In 426 women (age 69-98 years) who attended CAREDS2 follow-up visits (2016-2019), the ad-libitum use of L/Z supplements (≥ 1 mg/day) was associated with larger increases in MPOD over approximately 15 years since baseline (in healthy eyes and eyes with intermediate/advanced macular degeneration) and higher contrast sensitivity (limited to eyes without lens/retinal pathology). Using partial least squares (PLS) regression modeling, I further identified predictor phenotypes and genotypes permissive for the accumulation of macular pigment in women who use L/Z supplements, including greater neural retinal thickness in the fovea. Genetic variants that predict change in MPOD were identified in carotenoid-related candidate genes, including those that facilitate carotenoid absorption (SCARB1 and SCARB2), transport in the bloodstream (LIPC and ABCA1), and binding or metabolism in the retina (STARD3 and RPE65). Dietary recommendations to maximize macular pigment should focus on overall healthy diet patterns (e.g. the heart-healthy Mediterranean Diet pattern), which was associated with higher MPOD in CAREDS through the provision of L/Z in green-leafy vegetables, maintenance of healthy body composition and prevention of metabolic disease. These findings may inform recommendations designed to maximize MPOD in older adults to maintain normal vision for as long as possible, and to mitigate risk for age-related eye disease. Part IIPrimary open-angle glaucoma (POAG) is a common, irreversible neurodegenerative disease of the optic nerve that disproportionately affects older adults. While there are currently few modifiable risk factors for POAG, there is evidence that antioxidants (including L/Z in the retina as macular pigment) may confer protection. In Part II of this dissertation, I used data from the Carotenoids in Age-Related Eye Disease Study (CAREDS) to investigate whether macular pigment density (MPOD), measured at baseline (2001-2004) is associated with manifest primary open-angle glaucoma (POAG) approximately 15 years later in the CAREDS2 follow-up study (2016-2019). In 1258 eyes from participants who completed MPOD testing at CAREDS baseline and adjudication of POAG at CAREDS2, a non-linear protective trend was observed: participants in MPOD quartile 1 (vs. 2-4) were approximately 2x as likely to have POAG at CAREDS2 (p = .07). This association was strengthened in the subgroup of participants with stable MPOD (±0.20 density units) since baseline (p = .01). Notably, an association between MPOD and peripapillary retinal nerve fiber layer (RNFL) thickness (a marker of glaucomatous neurodegeneration in the optic nerve) was not observed. While the nature of this association is not clear, higher MPOD may reflect lifelong adherence to a diet rich in fruits and vegetables, which may have a protective role via mitigation of oxidative stress. In a separate analysis, a single measure of fruit and vegetable consumption at CAREDS baseline was associated with greater peripapillary RNFL thickness at CAREDS2, but was not associated with manifest POAG. We have also observed that higher levels of lutein and zeaxanthin (L/Z) in the retina (as macular pigment) and in the serum are positively associated with the diameter of arterioles and venules in the optic disc, suggesting that L/Z (or healthy diets rich in antioxidants) may be protective in glaucoma by influencing ocular blood flow. While additional longitudinal studies are needed to corroborate the association between MPOD at manifest POAG, our results add to a body of evidence suggesting that antioxidant rich diets containing adequate fruits and vegetables may have a protective role in glaucoma. If confirmed in independent studies, MPOD (which can be measured simply and non-invasively in the clinic) may be useful to identify individuals at elevated risk for POAG.
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