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Published on: November 19, 2011
Cathepsin H deficiency leads to myopic phenotype in mice
Hao Mou1, Haicheng She2, Chang-Jun Zhang2
1Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Science Key Laboratory, Beijing, 100730, China.
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.
Insights
Loss of the cathepsin H (CTSH) gene in mice causes high myopia. This study reveals CTSH
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Genetic factors are increasingly implicated in high myopia.
- A prior study linked cathepsin H (CTSH) gene mutations to high myopia.
- The function and characteristics of Ctsh-deficient mice were previously unknown.
Purpose of the Study:
- To investigate the role of cathepsin H (CTSH) in myopia development.
- To characterize the phenotype and mechanisms of Ctsh-deficient mice.
- To establish a Ctsh knockout mouse model for myopia research.
Main Methods:
- Generated a Ctsh knockout mouse model using CRISPR/Cas9 gene editing.
- Confirmed gene knockout via Sanger sequencing.
- Assessed refractive error using photorefraction and axial length via MRI.
- Evaluated retinal function with electroretinogram (ERG) and structure with optical coherence tomography (OCT).
- Analyzed retinal gene expression changes using RNA-sequencing (RNA-seq) and RT-PCR.
Main Results:
- Ctsh knockout mice exhibited a myopic shift and axial elongation.
- Reduced scotopic responses were observed in the electroretinogram (ERG) of knockout mice.
- Optical coherence tomography (OCT) revealed slight retinal thinning.
- Significant gene expression alterations were detected in the retinas of knockout mice.
Conclusions:
- Ctsh plays a critical role in the process of emmetropization.
- Loss-of-function mutations in CTSH contribute to the development of myopia.
- The Ctsh knockout mouse model provides a valuable tool for studying myopia pathogenesis.
