June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Diet, Aging and Retinal Homeostasis
Author Affiliations & Notes
  • Anupam Kumar Mondal
    National Eye Institute Neurobiology Neurodegeneration and Repair Laboratory, Bethesda, Maryland, United States
  • Daniel Brock
    National Eye Institute Neurobiology Neurodegeneration and Repair Laboratory, Bethesda, Maryland, United States
  • Jessica Gumerson
    National Eye Institute Neurobiology Neurodegeneration and Repair Laboratory, Bethesda, Maryland, United States
  • Ke Jiang
    National Eye Institute Neurobiology Neurodegeneration and Repair Laboratory, Bethesda, Maryland, United States
  • Jacob Nellissery
    National Eye Institute Neurobiology Neurodegeneration and Repair Laboratory, Bethesda, Maryland, United States
  • Emily Y Chew
    Division of Epidemiology and Clinical Applications, National Eye Institute, Bethesda, Maryland, United States
  • Anand Swaroop
    National Eye Institute Neurobiology Neurodegeneration and Repair Laboratory, Bethesda, Maryland, United States
  • Footnotes
    Commercial Relationships   Anupam Mondal None; Daniel Brock None; Jessica Gumerson None; Ke Jiang None; Jacob Nellissery None; Emily Chew None; Anand Swaroop None
  • Footnotes
    Support  NIH ODS Research Scholarship; NIH IRP ZIAEY000450, ZIAEY000546
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 1920 – A0066. doi:
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      Anupam Kumar Mondal, Daniel Brock, Jessica Gumerson, Ke Jiang, Jacob Nellissery, Emily Y Chew, Anand Swaroop; Diet, Aging and Retinal Homeostasis. Invest. Ophthalmol. Vis. Sci. 2022;63(7):1920 – A0066.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Aging is associated with declining vision and increased risk of age-related ocular diseases. In addition to genetics, extrinsic factors such as dietary habits have been linked to risk of retinal neurodegeneration, as shown by the AREDS1/2 clinical trials. We previously illustrated epigenetic changes as drivers of molecular aging in mouse rod photoreceptors and identified mitochondrial energy metabolism as a key process. However, the precise molecular networks through which aging and diet (nutrients) interact with retinal health remain poorly understood. We hypothesize that aging and lifestyle influence retinal homeostasis through epigenomic changes and altered cellular metabolism. This study employed a multi-omics strategy to characterize the role of nutrition in retinal aging.

Methods : A cohort of 12-month-old male and female C57BL6/J mice were fed (ad libitum) control chow (NIH-31) or one of four special diets: high-fat diet; Mediterranean diet; a custom diet with AREDS2 supplements; or supplementation of vitamins B6, B9 and B12. Supplements were tailored to mimic human allowance. After six-months, each group was subjected to electroretinography (ERG). The retinas were then isolated for Seahorse assays to determine metabolic status or for preparing RNA or DNA for transcriptome or whole genome methylation analyses, respectively.

Results : The control, AREDS and vitamin B groups showed a stable body weight over the treatment course. However, the high-fat and Mediterranean diets displayed remarkable weight gain, with prominent lead by female mice. ERG analysis revealed high variance, in both scotopic and photopic measures, among some of the groups, probably as a result of the ad libitum environment. No significant differences in ERG were detected between the treatments. Retinal extracellular acidification rate (glycolytic activity) and oxygen consumption rate (mitochondrial respiration) were impacted with age but the responses of diet groups and gender remain to be clarified conclusively. Transcriptome and methylation analyses are in progress.

Conclusions : Our study shows that nutritional habits can exert varying responses even in a controlled isogeneic setting. We predict that diet primes the retinal molecular/cellular landscape during aging either in favor or against disease development, with the final outcome being determined by divergent factors. Understanding the nexus between diet, aging, and retinal health is vital for preserving healthy vision.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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