Cathepsin H deficiency leads to myopic phenotype in mice

Abstract

Genetic predisposition has been increasingly reported in patients with high myopia. A previous study reported that a deleterious mutation in cathepsin H (CTSH) gene causes high myopia. However, the phenotypic and mechanistic characteristics of Ctsh-deficient mice remain unknown. In this study, we generated a Ctsh knockout mouse model using CRISPR/Cas9, and confirmed the abolishment of Ctsh by Sanger sequencing. In the mouse model, myopic shift was measured by photorefraction and axial elongation was detected by magnetic resonance imaging (MRI). Retinal function detected by electroretinogram (ERG) indicated the scotopic responses of knockout mice were reduced, and slight retinal thinning was observed using optical coherence tomography (OCT). In addition, ribonucleic acid sequencing (RNA-seq) and real-time polymerase chain reaction (RT-PCR) demonstrated gene expression changes in the retinas of knockout mice. Our results indicated that Ctsh plays an important role in emmetropization and that its loss-of-function leads to myopia development.