ArticleLaboratory investigation; a journal of technical methods and pathology2022
Characterization and identification of measurable endpoints in a mouse model featuring age-related retinal pathologies: a platform to test therapies.
Article in Laboratory investigation; a journal of technical methods and pathology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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5 citing papers in PubMed, 6 citations in OpenAlex.
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- Age- and sex- divergent translatomic responses of the mouse retinal pigmented epithelium.Neurobiology of aging · 2024Article
- Review
- Potential therapeutic targets for age-related macular degeneration: The nuclear option.Progress in retinal and eye research · 2023Review
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4 authors at 2 institutions in 1 country.
Funding
Abstract
Apolipoprotein B100 (apoB100) is the structural protein of cholesterol carriers including low-density lipoproteins. It is a constituent of sub-retinal pigment epithelial (sub-RPE) deposits and pro-atherogenic plaques, hallmarks of early dry age-related macular degeneration (AMD), an ocular neurodegenerative blinding disease, and cardiovascular disease, respectively. Herein, we characterized the retinal pathology of transgenic mice expressing mouse apoB100 in order to catalog their functional and morphological ocular phenotypes as a function of age and establish measurable endpoints for their use as a mouse model to test potential therapies. ApoB100 mice were found to exhibit an age-related decline in retinal function, as measured by electroretinogram (ERG) recordings of their scotopic a-wave, scotopic b-wave; and c-wave amplitudes. ApoB100 mice also displayed a buildup of the cholesterol carrier, apolipoprotein E (apoE) within and below the supporting extracellular matrix, Bruch's membrane (BrM), along with BrM thickening, and accumulation of thin diffuse electron-dense sub-RPE deposits, the severity of which increased with age. Moreover, the combination of apoB100 and advanced age were found to be associated with RPE morphological changes and the presence of sub-retinal immune cells as visualized in RPE-choroid flatmounts. Finally, aged apoB100 mice showed higher levels of circulating and ocular pro-inflammatory cytokines, supporting a link between age and increased local and systemic inflammation. Collectively, the data support the use of aged apoB100 mice as a platform to evaluate potential therapies for retinal degeneration, specifically drugs intended to target removal of lipids from Bruch's membrane and/or alleviate ocular inflammation.
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