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Project at Queen's University Belfast: Investigation of the capacity of a diet rich in lutein and zeaxanthin to increase macular pigment density, thereby potentially reducing the risk of age-related macular degeneration by dietary means.


   FoodBioSystems DTP

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  Prof J Woodside  No more applications being accepted  Funded PhD Project (UK Students Only)

About the Project

IMPORTANT NOTE: This project must start on or before 30 September 2021.

Research question

Can consuming a healthy plant food, rich in protective macular pigments, be a lifestyle strategy that has the potential to reduce the risk of age-related macular degeneration (AMD)?

 Hypothesis

Consumption of a diet rich in the xanthophylls, lutein and zeaxanthin, can increase protective macular pigment as effectively as a lutein/zeaxanthin supplement, thus potentially reducing the risk or progression of AMD by dietary means.

Background and Justification

AMD is the leading cause of blindness in developed countries1. In early AMD, waste material, known as drusen, builds up under the retina, the light-detecting layer in the eye1. Increasing size and number of drusen is associated with development of the late forms of AMD: geographic atrophy (GA) where there is gradual death of light-detecting cells and neovascular AMD (nAMD) where fragile blood vessels grow below and into the retina, causing bleeding. Both types lead to permanent vision loss and can occur together. Currently, the only effective treatment for nAMD is eye injections that help reduce vision loss. There are no known treatments to prevent the development of GA1.  

The macula is a specialised part of the retina, mediating central vision, providing the sharpest visual acuity and facilitating the best colour discrimination2. Macular pigment, as measured by macular pigment optical density (MPOD), is concentrated in the inner and central layers and is believed to protect against AMD2. It is mainly composed of the xanthophylls, lutein, zeaxanthin and meso-zeaxanthin (synthesised in situ from lutein)2. The concentration of these xanthophylls in the macula is 1000-fold greater than in the blood, demonstrating high selectivity. This suggests a pivotal role for the xanthophylls which are believed to play a major role in protecting the retina and retinal pigment epithelium from light-initiated oxidative damage by scavenging reactive oxygen species and filtering blue light2. The xanthophylls are transported on HDL and polymorphisms in HDL-related loci have been associated with AMD and plasma lutein/zeaxanthin3.

 Data from epidemiological studies suggests that dietary lutein and zeaxanthin intake are inversely associated with the risk of AMD. The AREDS2 randomised trial, carried out in the US, supplemented patients with early AMD with an antioxidant supplement that included lutein (10 mg) and zeaxanthin (2 mg). In a secondary analysis of that study, supplementation with lutein and zeaxanthin was protective against progression to late AMD in individuals with low lutein/zeaxanthin intake4. A meta-analysis of 19 studies showed that supplementation with lutein and/or zeaxanthin and/or meso-zeaxanthin improved MPOD both in AMD patients and healthy subjects, with a dose-response relationship2. However, not all studies have shown an effect of lutein/zeaxanthin supplementation on MPOD5,6. The proposed research will address that uncertainty.

What the student will do:

  • Search the literature to review the evidence for an effect of lutein/zeaxanthin and associated factors on AMD risk and progression.
  • In collaboration with Professor Paul Fraser, Head of the Plant Molecular Sciences group at Royal Holloway (and Syngenta), select non-GMO Capsicum varieties that are rich in lutein and zeaxanthin.
  • Analyse the two selected Capsicum varieties for lutein, zeaxanthin, beta-carotene and vitamin C.
  • Work with Odysea to produce jars of the selected flame-roasted dark-orange Capsicum in brine.
  • Recruit volunteers with a family history (therefore at significantly increased risk) of AMD who will agree to consume approximately ½ a Capsicum per day (either the selected fresh or bottled variety), or a lutein/zeaxanthin supplement (as a comparator). 
  • Measure their dietary intake (including lutein/zeaxanthin) by food-frequency questionnaire (FFQ).
  • Organise the measurement of macular pigment optical density (MPOD) at baseline and after 13 and 26 weeks of consumption of the Capsicum-rich diet vs. the supplement in the volunteers.
  • Measure lutein, zeaxanthin and cholesterol in blood serum at baseline, 3 and 6 months. 

Training opportunities:

With Prof Paul Fraser’s group in Royal Holloway, University of London (RHUL), to learn about strategies used in crop breeding (in collaboration with Syngenta);

With RHUL to carry out the analysis of carotenoids/xanthophylls pigments in Capsicum by HPLC-PDA;

With Odysea to learn about Capsicum harvesting, preparation and bottling.

The student will:

  •  learn the principles of breeding Capsicum to optimise xanthophyll production
  • obtain ethics permission for a human study
  • recruit at-risk volunteers to a dietary intervention
  •  measure: Capsicum concentrations of lutein/zeaxanthin, carotene and vitamin C, plasma lutein/zeaxanthin, fat mass (a confounder of lutein/zeaxanthin bioavailability) by bioelectrical impedance
  • organise measurement of MPOD by state-of-the-art method (see figure)
  • modify and analyse an existing UK-validated FFQ so it can capture lutein/zeaxanthin intake
  • design and analyse other questionnaires that can identify confounders
  • learn how to harvest, process and bottle Capsicum in brine
  • learn the methodology of public health/epidemiology/medical statistics
  • understand the pathology, causes and treatment of AMD

Student profile

This project is suitable for a student with a degree in nutrition, chemistry, agriculture, food science or a closely related science who has an interest in diet and health. He/she should have laboratory skills, be able to write well and already have, or expect to obtain, a minimum of an upper second class honours degree. The student will be based at Queen’s University Belfast but will be expected to spend up to 12 months in total at the University of Surrey.

How to apply

Only candidates who are eligible for home student status and who are able for a start date on or before 30 September 2021 should apply for this studentship.

Applications must be submitted on our online application portal https://foodbiosystemsdtp.grantplatform.com/

More details about the application and selection process are available from the FoodBioSystems DTP website

Please do not submit a CV it will not be used in the selection process.

Interviews for shortlisted candidates will be held on 19 August 2021.


Funding Notes

This studentship is open to students who meet UK home student status. To be classed as a home student, candidates must meet the following criteria:
• Be a UK National (meeting residency requirements), or
• Have settled status, or
• Have pre-settled status (meeting residency requirements), or
• Have indefinite leave to remain or enter
The funding will include a tax free stipend and support for tuition fees at the standard UK rate (in 2021/2022 this is a minimum of £15,609 per year and £4500 per year respectively). There will also be a contribution towards research costs.

References

1. SanGiovanni & Neuringer. Am J Clin Nutr 2012; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471204/pdf/ajcn9651223S.pdf
2. Ma et al. Nutrients 2016; https://www.mdpi.com/2072-6643/8/7/426
3. Koo et al. Am J Clin Nutr 2014; https://academic.oup.com/ajcn/article/100/suppl_1/336S/4576438
4. Chew et al. JAMA Opthalmol 2014; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636082/pdf/nihms720274.pdf
5. Korobelnik et al. JAMA Ophthalmol 2017; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710391/
6. Lin et al. Opthalmic Epidemiol 2017; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6025894/pdf/nihms975420.pdf