Academic Journal
ApoE- and Cfh-deficient mice exhibit structural and molecular features of human early-intermediate retinal degeneration.
| Τίτλος: | ApoE- and Cfh-deficient mice exhibit structural and molecular features of human early-intermediate retinal degeneration. |
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| Συγγραφείς: | Recalde S; Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research, IdiSNA, Pamplona, Spain., Moreno Orduña M; Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain., Bezunartea J; Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain., Belza I; Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain., Chas A; Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain., Fernández-Sánchez L; Department of Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain.; Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain., Cuenca Navarro N; Department of Optics, Pharmacology and Anatomy, University of Alicante, Alicante, Spain.; Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain., García-Layana A; Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research, IdiSNA, Pamplona, Spain., Fernández-Robredo P; Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research, IdiSNA, Pamplona, Spain., Hernández M; Retinal Pathologies and New Therapies Group, Experimental Ophthalmology Laboratory, Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research, IdiSNA, Pamplona, Spain. |
| Πηγή: | Animal models and experimental medicine [Animal Model Exp Med] 2026 Jul; Vol. 9 (7), pp. 1420-1435. Date of Electronic Publication: 2026 Jul 01. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: John Wiley & Sons, Inc Country of Publication: United States NLM ID: 101726292 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2576-2095 (Electronic) Linking ISSN: 25762095 NLM ISO Abbreviation: Animal Model Exp Med Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Hoboken, New Jersey] : John Wiley & Sons, Inc., [2018]- |
| Ιατρικοί όροι (MeSH): | Apolipoproteins E*/genetics , Apolipoproteins E*/deficiency , Complement Factor H*/deficiency , Complement Factor H*/genetics , Retinal Degeneration*/pathology , Retinal Degeneration*/genetics , Macular Degeneration*/pathology , Macular Degeneration*/genetics, Retinal Pigment Epithelium/pathology ; Retinal Pigment Epithelium/ultrastructure ; Bruch Membrane/pathology ; Retina/pathology ; Animals ; Disease Models, Animal ; Mice ; Mice, Knockout ; Humans ; Lipid Metabolism ; Mice, Inbred C57BL |
| Περίληψη: | 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. (© 2026 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.) |
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| Grant Information: | RD21/0002/0010 Inflammatory Disease Network; SAF2016-81876-REDT Red Nacional de Investigación en Complemento; Fundación Gangoiti (Spain); Fundación Multiópticas (Spain) |
| Contributed Indexing: | Keywords: Bruch's membrane; aged macular degeneration; animal model; apolipoprotein E; complement factor H; inflammation; lipid metabolism; retinal pigment epithelium |
| Substance Nomenclature: | 0 (Apolipoproteins E) 80295-65-4 (Complement Factor H) |
| Entry Date(s): | Date Created: 20260701 Date Completed: 20260730 Latest Revision: 20260813 |
| Update Code: | 20260814 |
| PubMed Central ID: | PMC13394217 |
| DOI: | 10.1002/ame2.70243 |
| PMID: | 42383569 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 2576-2095 |
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| DOI: | 10.1002/ame2.70243 |