Animal Models and Experimental Medicine · Published 2026-07-01 · DOI 10.1002/ame2.70243
Sergio Recalde, Maite Moreno Orduña, Jaione Bezunartea, Idoia Belza, Ainara Chas, Laura Fernández‐Sánchez, Nicolás Cuenca Navarro, Alfredo García‐Layana, Patricia Fernández‐Robredo, María Hernández
Abstract Background Age‐related macular degeneration (AMD) is a multifactorial retinal disease in which alterations in lipid metabolism and dysregulation of the complement system play a central role. The aim of this study was to characterize a novel double‐knockout (DK) mouse model deficient in apolipoprotein E and complement factor H (ApoE−/–Cfh−/−) as an experimental model of early and intermediate AMD. Methods ApoE−/–Cfh−/− mice and wild‐type controls underwent comprehensive morphological, ultrastructural, biochemical, and molecular analyses. Retinal and retinal pigment epithelium (RPE) integrity, Bruch's membrane (BM) morphology, lipid accumulation, complement activation, angiogenic signaling, and synaptic organization were evaluated using histology, electron microscopy, immunohistochemistry, biochemical assays, and gene expression analyses. Results DK mice exhibited significant RPE thinning, disruption of tight junctions, vacuolization, and BM thickening (p < 0.05). Lipid accumulation and plasma lipid levels significantly increased compared with controls (p < 0.01). Complement activation was significantly enhanced, as evidenced by increased C5b‐9 deposition (p < 0.01). In addition, DK mice exhibited increased vascular endothelial growth factor expression (p < 0.05), altered matrix metalloproteinase activity (p < 0.05), and significant synaptic disorganization between photoreceptors and second‐order neurons (p < 0.05). Conclusions The ApoE−/–Cfh−/− mouse reproduces key molecular and structural features of early and intermediate retinal degeneration with statistically significant alterations. Although it does not progress to advanced disease stages, it represents a valuable model to investigate several factors of AMD pathogenesis and evaluate therapeutic strategies targeting early disease mechanisms.
Abstract from DOAJ. Public domain (CC0 1.0).
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Recalde, S., Orduña, M., Bezunartea, J., et al. (2026). ApoE ‐ and Cfh‐deficient mice exhibit structural and molecular features of human early–intermediate retinal degeneration. Animal Models and Experimental Medicine. https://doi.org/10.1002/ame2.70243