June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
A Systemic Pharmacology Analysis of the Age-Related Eye Disease Study 2 (AREDS2) formula and its role in preventing Age-Related Macular Degeneration (AMD)
Author Affiliations & Notes
  • Miki Wang
    Paul L. Foster School of Medicine, El Paso, Texas, United States
  • Yu Yu
    Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Alexander Lou
    The Village School, Houston, Texas, United States
  • Luis Aguilera Garcia
    University of North Texas System College of Pharmacy, Fort Worth, Texas, United States
  • Myhoa Tran
    University of North Texas System College of Pharmacy, Fort Worth, Texas, United States
  • Anh Duong
    University of North Texas System College of Pharmacy, Fort Worth, Texas, United States
  • Hongli Wu
    Pharmaceutical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, United States
    North Texas Eye Researc Institute, University of North Texas Health Science Center, Fort Worth, Texas, United States
  • Footnotes
    Commercial Relationships   Miki Wang, None; Yu Yu, None; Alexander Lou, None; Luis Garcia, None; Myhoa Tran, None; Anh Duong, None; Hongli Wu, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4923. doi:
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      Miki Wang, Yu Yu, Alexander Lou, Luis Aguilera Garcia, Myhoa Tran, Anh Duong, Hongli Wu; A Systemic Pharmacology Analysis of the Age-Related Eye Disease Study 2 (AREDS2) formula and its role in preventing Age-Related Macular Degeneration (AMD). Invest. Ophthalmol. Vis. Sci. 2020;61(7):4923.

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

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  • Supplements
Abstract

Purpose : According to the major clinical trial sponsored by the National Eye Institute (NEI), oral supplementation with the Age-Related Eye Disease Study 2 (AREDS2) formulation (vitamins C and E, zinc, copper, lutein, and zeaxanthin) has been shown to delay the progression of advanced age-related macular degeneration (AMD). However, the detailed pharmacological mechanisms of AREDS2 have not been fully understood at the molecular level, other than its well-known antioxidative effects. In this study, we intend to develop a systemic approach to predict the AREDS2-associated targets and to build the drug-disease-target network.

Methods : Genes of interest were identified via the NCBI database for all the compounds in the AREDS2 formula. Cytoscape software was used to visually create a network of source and target nodes to analyze the similarities between the nodes. This allowed a map of the most common diseases, pathways, functions, and processes of the compounds in AREDS2 to be created. The formula’s relation to AMD was analyzed via the Gene2Function and GeneCard databases. Cytoscape was once again used to identify major pathways that the AREDS2 formula targeted.

Results : A total of 158 genes were identified to be the targets of the AREDS2 formula. 27 out of the 158 genes were a result of multiple components of the AREDS2 formula. The main pathways that these genes affect were identified and mapped out to include adipogenesis, angiogenesis, apoptosis cascade, DNA damage response, fluid shear stress and atherosclerosis, glutathione metabolism, HIF1 signaling pathway, innate immune pathway, lipoprotein metabolism, Nrf2 pathway, oxidative stress, photodynamic therapy induced survival signaling, regulation of lipid metabolism, response to hypoxia, and the statin pathway. The top 5 genes regulated by the most components of the AREDS2 formula are GSTP1, Nrf2, VEGFA, HIF1A, and CXCL8.

Conclusions : The systemic pharmacology-based approach provides beneficial information for elucidating the potential mechanisms of action of the AREDS2 formula in treating AMD. Most importantly, it provides future directions for AMD treatment which may focus on anti-adipogenic, anti-inflammation, and anti-oxidant pathways.

This is a 2020 ARVO Annual Meeting abstract.

 

 

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