Immunohistochemical Profiling of Corneas With Fuchs Endothelial Corneal Dystrophy
An-Katrien De Roo1, Thomas Janssens, Beatrijs Foets
1*Laboratory for Translational Cell & Tissue Research, Department of Imaging & Pathology, KU Leuven-University of Leuven, Leuven, Belgium; †Department of Pathology, UZ Leuven-University Hospitals Leuven, Leuven, Belgium; ‡Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven-University of Leuven, Leuven, Belgium; §Department of Ophthalmology, UZ Leuven-University Hospitals Leuven, Leuven, Belgium; and ¶Research Group Ophthalmology, Department of Neurosciences, KU Leuven-University of Leuven, Leuven, Belgium.
Purpose:
Fuchs endothelial corneal dystrophy (FECD) is the leading indication for endothelial keratoplasty. Further insight into its pathophysiology is needed to develop alternative therapies.
Methods:
Sixteen genes from a previous microarray expression experiment (FECD vs. normal) were validated using immunohistochemistry on paraffin-embedded corneas (n = 6 FECD, n = 6 normal). The results were quantified manually and semiautomatically.
Results:
A higher percentage of corneal endothelial cells stained for alpha-smooth muscle actin (αSMA), cytokeratin 7, and superoxide dismutase 3 in FECD versus normal [odds ratios (ORs) of 60.90, 41.70, and 15.16, respectively, P < 0.001]. Dot-like staining for major histocompatibility complex, class II, DR alpha was present in FECD, but not in normal. Higher percentages of stromal cells in FECD versus normal stained for αSMA (OR = 864.26, P < 0.001), brain-derived neurotrophic factor (BDNF, OR = 6.34, P = 0.005), fibroblast growth factor 7 (FGF-7, OR = 2.76, P = 0.011), FGF-9 (OR = 5.97, P < 0.001), receptor FGFR-3 (OR = 13.90, P = < 0.001), and serum amyloid A1 (OR = 3.45, P = 0.023). Higher percentages of corneal epithelial cells stained for αSMA (OR = 2.20, P = 0.006) and BDNF (OR = 3.94, P < 0.001) in FECD versus normal.
Conclusions:
These results support a role for epithelial-mesenchymal transition (αSMA), oxidative stress (superoxide dismutase 3), and major histocompatibility complex, class II, DR alpha cells with dendritic morphology in the pathophysiology of FECD. Furthermore, corneal stromal cells express trophic molecules (BDNF and FGFs) and markers of chronic inflammation (serum amyloid A1) in FECD.
Insights
Fuchs endothelial corneal dystrophy (FECD) involves epithelial-mesenchymal transition, oxidative stress, and inflammation. These findings in corneal cells offer new therapeutic targets for FECD, a leading cause of corneal transplants.
Area of Science:
- Ophthalmology
- Corneal Diseases
- Cell Biology
Background:
- Fuchs endothelial corneal dystrophy (FECD) is a primary indication for endothelial keratoplasty.
- Understanding FECD's pathophysiology is crucial for developing alternative treatments.
Purpose of the Study:
- To investigate the molecular mechanisms underlying FECD.
- To identify potential biomarkers and therapeutic targets for FECD.
Main Methods:
- Validated gene expression from a previous microarray experiment using immunohistochemistry.
- Analyzed protein expression in corneal tissues from FECD and normal donors.
- Quantified staining results manually and semiautomatically.
Main Results:
- Elevated expression of alpha-smooth muscle actin (αSMA), cytokeratin 7, and superoxide dismutase 3 in FECD corneal endothelial cells.
- Presence of MHC class II DR alpha in FECD endothelial cells, absent in normal controls.
- Increased αSMA, BDNF, FGFs, and serum amyloid A1 in FECD stromal and epithelial cells.
Conclusions:
- Epithelial-mesenchymal transition (αSMA), oxidative stress (superoxide dismutase 3), and dendritic MHC class II DR alpha cells contribute to FECD pathophysiology.
- Corneal stromal cells in FECD express trophic factors (BDNF, FGFs) and inflammation markers (serum amyloid A1).
- These findings highlight potential therapeutic avenues for FECD.
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