Cathepsin H deficiency leads to myopic phenotype in mice

Topics:

Myopia

Myopia, Refractive Development and Eye Growth

Publication

Experimental Eye Research (Sep 01, 2025) Cathepsin H deficiency leads to myopic phenotype in mice

Mou H, She H, Zhang CJ, Li M, Wang W, Sun SN, Zhang X, Jin ZB

DOI: 10.1016/j.exer.2025.110447 >>

Mou et al developed a new mouse model for myopia studies, Cathepsin H knockout mice. They exhibit a clear myopic phenotype, characterized by increased axial length and a myopic shift in refractive error, as shown by Striatech’s Photorefractor. These structural changes are accompanied by reduced scotopic retinal responses, mild retinal thinning, and altered expression of genes linked to Notch signaling. The data indicate that cathepsin H is required for normal emmetropization, and its loss perturbs molecular pathways that regulate ocular growth, predisposing to myopia.

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.