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CLRN1 Variants in Müller Cells Cause Mitochondrial Dysfunction in USH3A Retinal Organoids
Rui Zhang1,2, Xinbo Ji2, Han Yu1
1Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, China.
CNS Neuroscience & Therapeutics
|August 3, 2026
Summary
Mutations in the CLRN1 gene cause Usher syndrome 3A (USH3A), leading to retinitis pigmentosa. This study reveals CLRN1-related mitochondrial dysfunction in Müller cells drives retinal degeneration, offering new therapeutic targets.
Area of Science:
- Ophthalmology
- Genetics
- Cell Biology
Background:
- Usher syndrome 3A (USH3A) involves retinitis pigmentosa and hearing loss, linked to CLRN1 gene mutations.
- The precise role of CLRN1 in retinal degeneration is not fully understood.
Purpose of the Study:
- Investigate the role of CLRN1 in retinal degeneration in USH3A.
- Determine the impact of CLRN1 variants on retinal cells.
- Evaluate idebenone as a potential therapy for USH3A.
Main Methods:
- Utilized patient-derived retinal organoids for single-cell RNA sequencing and electrophysiological recordings.
- Mapped CLRN1 expression in human retina and organoids.
- Assessed the effects of CLRN1 variants on Müller cells and photoreceptors.
Main Results:
- CLRN1 is expressed in Müller cells; variants cause retinal degeneration.
- CLRN1 variants induce Müller cell mitochondrial dysfunction, leading to photoreceptor apoptosis.
- Idebenone treatment showed partial rescue of retinal deficits.
Conclusions:
- Müller cell mitochondrial dysfunction is a key mechanism in USH3A-related retinitis pigmentosa.
- CLRN1 variants impair Müller cell mitochondria, impacting photoreceptor health.
- Targeting Müller cell mitochondria presents a potential therapeutic strategy for USH3A.
