An-Katrien De Roo1, Jasper Wouters2, Olivier Govaere3, Beatrijs Foets4, Joost J van den Oord1. 1. Department of Imaging & Pathology, Laboratory for Translational Cell & Tissue Research, KU Leuven - University of Leuven, Leuven, Belgium 2Department of Pathology, UZ Leuven - University Hospitals Leuven, Leuven, Belgium. 2. Department of Pathology, UZ Leuven - University Hospitals Leuven, Leuven, Belgium. 3. Department of Imaging & Pathology, Laboratory for Translational Cell & Tissue Research, KU Leuven - University of Leuven, Leuven, Belgium 3Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom. 4. Department of Ophthalmology, UZ Leuven - University Hospitals Leuven, Leuven, Belgium 5Department of Neurosciences, Research Group Ophthalmology, KU Leuven - University of Leuven, Leuven, Belgium.
Abstract
Purpose: Fuchs' endothelial corneal dystrophy (FECD) is a degenerative eye disorder affecting 4% of Americans older than 40. It is the leading indication for corneal endothelial (CE) transplantation for which there is a global donor shortage. This study aimed to gain further insight into the pathophysiology of FECD and identify targets for nonsurgical therapy. Methods: CE from patients with late-onset FECD was compared with that of normal controls using microarray expression analysis (n = 4 FECD, n = 4 normal), reverse transcriptase quantitative PCR (n = 9 FECD, n = 8 normal), and immunohistology (n = 55 FECD, n = 15 normal). Results: This led to the identification of circulating fibrocytes and their dendritic derivatives in all examined CE samples with FECD (in all clinical stages of symptomatic FECD and independent of prior cataract surgery). These cells were not present in normal CE. In this study we characterize their morphology, protein expression profile, number, and localization within the CE layer of patients with FECD. Conclusions: Circulating fibrocytes and their dendritic derivatives are a new aspect of FECD that deserves further investigation. Because they are known to cause fibrosis in a variety of organs, they may play a similar role in FECD and might be a valuable target for nonsurgical therapy.
Purpose: Fuchs' endothelial corneal dystrophy (FECD) is a degenerative eye disorder affecting 4% of Americans older than 40. It is the leading indication for corneal endothelial (CE) transplantation for which there is a global donor shortage. This study aimed to gain further insight into the pathophysiology of FECD and identify targets for nonsurgical therapy. Methods: CE from patients with late-onset FECD was compared with that of normal controls using microarray expression analysis (n = 4 FECD, n = 4 normal), reverse transcriptase quantitative PCR (n = 9 FECD, n = 8 normal), and immunohistology (n = 55 FECD, n = 15 normal). Results: This led to the identification of circulating fibrocytes and their dendritic derivatives in all examined CE samples with FECD (in all clinical stages of symptomatic FECD and independent of prior cataract surgery). These cells were not present in normal CE. In this study we characterize their morphology, protein expression profile, number, and localization within the CE layer of patients with FECD. Conclusions: Circulating fibrocytes and their dendritic derivatives are a new aspect of FECD that deserves further investigation. Because they are known to cause fibrosis in a variety of organs, they may play a similar role in FECD and might be a valuable target for nonsurgical therapy.
Authors: Yongjun Chu; Jiaxin Hu; Hanquan Liang; Mohammed Kanchwala; Chao Xing; Walter Beebe; C Bradley Bowman; Xin Gong; David R Corey; V Vinod Mootha Journal: Nucleic Acids Res Date: 2020-07-09 Impact factor: 16.971