ArticleInvestigative ophthalmology & visual science2013
L450W and Q455K Col8a2 knock-in mouse models of Fuchs endothelial corneal dystrophy show distinct phenotypes and evidence for altered autophagy.
Article in Investigative ophthalmology & visual science, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Autophagy modulation in animal models of corneal diseases: a systematic review.Molecular and cellular biochemistry · 2020Pooled it
- An Optimized Mechanical Peeling Protocol for Mouse Corneal Endothelium.Bioengineering (Basel, Switzerland) · 2026Article
- Review
- Exploring the histopathological signature of repeat-mediated Fuchs endothelial corneal dystrophy.Acta ophthalmologica · 2026Article
- Targeted AAV6 gene therapy restores corneal endothelial function in three hereditary corneal dystrophies.Cell reports. Medicine · 2026Article
- TAZ (bioRxiv : the preprint server for biology · 2026Article
- Autophagy in ocular diseases: from mechanisms to therapeutic potential.Frontiers in cell and developmental biology · 2026Review
- Heterozygous Tcf4 Deficiency Mitigates Fuchs Endothelial Corneal Dystrophy Progression in a Mouse Model.Investigative ophthalmology & visual science · 2025Article
- Review
- Article
- Endoplasmic Reticulum-Mitochondria Crosstalk in Fuchs Endothelial Corneal Dystrophy: Current Status and Future Prospects.International journal of molecular sciences · 2025Review
- Squishy matters - Corneal mechanobiology in health and disease.Progress in retinal and eye research · 2024Review
- Animal Models in Eye Research: Focus on Corneal Pathologies.International journal of molecular sciences · 2023Review
- Corneal Endothelial-like Cells Derived from Induced Pluripotent Stem Cells for Cell Therapy.International journal of molecular sciences · 2023Review
- Genome editing in the treatment of ocular diseases.Experimental & molecular medicine · 2023Review
- Mice Deficient in TAZ (Wwtr1) Demonstrate Clinical Features of Late-Onset Fuchs' Endothelial Corneal Dystrophy.Investigative ophthalmology & visual science · 2023Article
- The soil and the seed: The relationship between Descemet's membrane and the corneal endothelium.Experimental eye research · 2023Review
- AUTOPHAGY IN THE EYE: FROM PHYSIOLOGY TO PATHOPHYSOLOGY.Autophagy reports · 2023Article
- The roles of autophagy and mitophagy in corneal pathology: current knowledge and future perspectives.Frontiers in medicine · 2023Review
- Autophagy in the normal and diseased cornea.Experimental eye research · 2022Review
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeWe compared the cellular phenotypes and studied the role of autophagy in the pathogenesis of Fuchs endothelial corneal dystrophy (FECD) using two α2 collagen VIII (Col8a2) knock-in mouse models and human FECD tissues.
methodsIn vivo corneal endothelial cell (CEC) counts and morphology were analyzed by clinical confocal microscopy. Ultrastructural analysis of CECs was performed by transmission electron microscopy. Real-time PCR and Western blotting were performed using total RNA, and protein extracted from mouse CECs and human CECs obtained from FECD and autopsy patients.
resultsBoth Col8a2 mouse models exhibited hallmarks of FECD; however, the Col8a2(L450W/L450W) mice exhibited a milder phenotype compared to the Col8a2(Q455K/Q455K) mice. Both models exhibited upregulation of the unfolded protein response (UPR) as evidenced by dilated rough endoplasmic reticulum (RER), and upregulation of UPR-associated genes and proteins. Real-time PCR of Col8a2(L450W/L450W) and Col8a2(Q455K/Q455K) CECs at 40 weeks revealed a 2.1-fold (P < 0.05) and a 5.2-fold (P < 0.01) upregulation of the autophagy marker Dram1, respectively. Real-time PCR of human FECD endothelium revealed a 10.4-fold upregulation of DRAM1 (P < 0.0001) compared to autopsy controls.
conclusionsThe Col8a2(L450W/L450W) and Col8a2(Q455K/Q455K) mouse models of FECD showed distinct endothelial cell phenotypes. Dram1 was associated with activation of the UPR and increased autophagy. Overexpression of this gene in mouse and human FECD endothelial cells suggested a role for altered autophagy in this disease.
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