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- W4379093457 abstract "Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly, and there is currently no clinical treatment targeting the primary impairment of AMD. The earliest clinical hallmark of AMD is drusen, which are yellowish spots mainly composed of lipid droplets (LDs) accumulated under the retinal pigment epithelium (RPE). However, the potential pathogenic role of this excessive LD accumulation in AMD is yet to be determined, partially due to a lack of chemical tools to manipulate LDs specifically. Here, we employed our recently developed Lipid Droplets·AuTophagy Tethering Compounds (LD∙ATTECs) to degrade LDs and to evaluate its consequence on the AMD-like phenotypes in apoe-/- (apolipoprotein E; B6/JGpt-Apoeem1Cd82/Gpt) mouse model. apoe-/- mice fed with high-fat diet (apoe-/--HFD) exhibited excessive LD accumulation in the retina, particularly with AMD-like phenotypes including RPE degeneration, Bruch's membrane (BrM) thickening, drusen-like deposits, and photoreceptor dysfunction. LD·ATTEC treatment significantly cleared LDs in RPE/choroidal tissues without perturbing lipid synthesis-related proteins and rescued RPE degeneration and photoreceptor dysfunction in apoe-/--HFD mice. This observation implied a causal relationship between LD accumulation and AMD-relevant phenotypes. Mechanically, the apoe-/--HFD mice exhibited elevated oxidative stress and inflammatory signals, both of which were mitigated by the LD·ATTEC treatment. Collectively, this study demonstrated that LD accumulation was a trigger for the process of AMD and provided entry points for the treatment of the initial insult of AMD by degrading LDs.Abbreviations: AMD: age-related macular degeneration; APOE: apolipoprotein E; ATTECs: autophagy-tethering compounds; BODIPY: boron-dipyrromethene; BrM: Bruch's membrane; ERG: electroretinogram; HFD: high-fat diet; LD·ATTECs: Lipid Droplets·AuTophagy Tethering Compounds; LDs: lipid droplets; OA: oleic acid; OPL: outer plexiform layer; ROS: reactive oxygen species; RPE: retinal pigment epithelium." @default.
- W4379093457 created "2023-06-03" @default.
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- W4379093457 date "2023-06-05" @default.
- W4379093457 modified "2023-10-11" @default.
- W4379093457 title "Clearance of lipid droplets by chimeric autophagy-tethering compound ameliorates the age-related macular degeneration phenotype in mice lacking APOE" @default.
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- W4379093457 cites W1963621262 @default.
- W4379093457 cites W1972444897 @default.
- W4379093457 cites W1975901800 @default.
- W4379093457 cites W1979228140 @default.
- W4379093457 cites W1988804690 @default.
- W4379093457 cites W1991840137 @default.
- W4379093457 cites W1994239015 @default.
- W4379093457 cites W1994527422 @default.
- W4379093457 cites W1998406682 @default.
- W4379093457 cites W2001720244 @default.
- W4379093457 cites W2009053500 @default.
- W4379093457 cites W2013664728 @default.
- W4379093457 cites W2014694860 @default.
- W4379093457 cites W2020391754 @default.
- W4379093457 cites W2025176768 @default.
- W4379093457 cites W2041745079 @default.
- W4379093457 cites W2043234667 @default.
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- W4379093457 cites W2982548291 @default.
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- W4379093457 cites W3138156139 @default.
- W4379093457 cites W3138186090 @default.
- W4379093457 cites W3182522393 @default.
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- W4379093457 doi "https://doi.org/10.1080/15548627.2023.2220540" @default.
- W4379093457 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37266932" @default.
- W4379093457 hasPublicationYear "2023" @default.
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