Molecular studies of miR-29 associated deposition of extracellular matrix in Fuchs endothelial corneal dystrophy

点击翻译按钮获取中文摘要

Fuchs endothelial corneal dystrophy (FECD) is a bilateral disorder of the corneal endothelium and among the most common reasons for corneal transplant surgery in the Western world. So far, there are no established conservative treatments available. Morphologically, FECD is characterized by a decrease in corneal endothelial cell density with abnormal subendothelial deposition of extracellular matrix (ECM) progressing over several decades.MicroRNAs (miRNAs) are short non-coding RNAs and regulate gene expression at the post-transcriptional level. The miR-29 family is an important modulator of ECM homeostasis. In a previous study we have demonstrated for the first time significantly reduced expression of the miR-29 family with reciprocal overexpression of miR-29 target transcripts COL1A1 and COL4A1 and subendothelial deposition of the corresponding proteins in FECD endothelium.The proposed project will further investigate the hypothesis that reduced miR-29 expression leads to abnormal expression of ECM-related genes with unphysiological subendothelial deposition of ECM in FECD eyes.FECD endothelial samples will be assayed for expression of additional miR-29 associated ECM components. Subsequently, the effect of changes in miR-29 on ECM components in CECs will be analyzed in vitro. Finally, the expression of miR-29 and miR-29 associated ECM components in vivo will be studied in the worldwide first transgenic Col8a2Q455K/Q455K mutant mouse model of FECD.The proposed project will contribute to an improved understanding of the role of the miR-29 family in FED pathogenesis and will serve as a basis for the development of new conservative therapies.