Eye / Vision
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/29926
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Browsing Eye / Vision by Author "Duong, Anh"
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Item A Systemic Pharmacology Analysis of the Age-Related Eye Disease Study 2 (AREDS2) formula and its role in preventing Age-Related Macular Degeneration (AMD)(2020) Wu, Hongli; Yu, Yu; Lou, Alexander; Garcia, Luis; Tran, Myhoa; Duong, Anh; Wang, Miki; Brown, EricaPurpose: 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 compounds in the AREDS2 formula. Cytoscape software was used to visually create a network of source and target nodes to analyze similarities between nodes. Cytoscape was again used to identify major pathways the AREDS2 formula targeted. Results: A total of 158 genes were identified to be targets of the AREDS2 formula. 27 out of 158 genes were a result of multiple components of the AREDS2 formula. The main pathways 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 and oxidative stress pathway. The top 5 target genes were GSTP1, Nrf2, VEGFA, HIF1A, and CXCL8. Conclusion: The systemic pharmacology-based approach provides beneficial information for elucidating the potential mechanisms of action of the AREDS2 formula in treating AMD.Item Emerging functional crosstalk between the glutaredoxin system and Nrf2 antioxidant pathway: evidence from ultraviolet radiation-induced cataract formation(2020) Yu, Yu; Lou, Alexander; Garcia, Luis; Tran, Myhoa; Duong, Anh; Wu, Hongli; Liu, XiaobinPurpose: To determine the function of glutaredoxin (Grx) system, both glutaredoxin 1 (Grx1) and glutaredoxin 2 (Grx2), in protecting the lens against ultraviolet (UV)-induced cataract formation by using Grx1/Grx2 double knockout (DKO) mice as a model. Methods: One-month old Grx1/Grx2 DKO and age-matched wild-type (WT) mice were exposed to UV radiation to induce cataracts. Mice were euthanized at 4 days post-exposure. The degree of the cataract and lens morphology were evaluated under a dissecting microscope. Glutathione (GSH), free protein thiol(PSH), and protein glutathionylation (PSSG) levels were measured as general markers of oxidative damage. Nrf2 and its downstream target proteins were examined using Western blot. Results: We found that UV radiation caused more severe anterior subcapsular cataract in Grx1/Grx2 DKO than that of WT mice. The opacity of the lenses in DKO mice appeared to extend deeper into the cortical and even nuclear regions. Lenses of Grx1/Grx2 DKO mice contained significant lower levels of GSH and PSH. On the other hand, the accumulation of PSSG was much higher in Grx1/Grx2 DKO group. Deletion of Grx1 and Grx2 also decreased the expression of antioxidant enzyme transcription factor regulator, Nrf2, and its downstream antioxidant genes, including catalase, superoxide dismutase (SOD), and another redox regulator of thioredoxin (Trx). These changes were especially extensive in the lens after UV exposure. Conclusions: With combined Grx1 and Grx2 deletion, the Nrf2-dependent antioxidant response is severely impaired, causing elevation of oxidative stress that may increase the lens susceptibility to UV-induced damage.