ArticleInvestigative ophthalmology & visual science2026
Müller Glia-Exclusive CLRN1 Expression Drives Non-Cell-Autonomous Photoreceptor Degeneration in Usher Syndrome Type 3A.
Article in Investigative ophthalmology & visual science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Usher syndrome type 3A (USH3A), caused by CLRN1 mutations, leads to progressive deaf-blindness. Although CLRN1 expression has been localized to Müller glia (MG), the pathogenic mechanisms linking glial CLRN1 deficiency to photoreceptor death remain undefined. We utilized a novel large-animal model to elucidate cell-type-specific pathogenesis at single-nucleus resolution. Methods: CLRN1-/- rabbits were generated via CRISPR/Cas9. Retinal phenotyping included longitudinal optical coherence tomography (OCT), electroretinography (ERG), and histology for up to 3 years. Single-nucleus RNA sequencing (snRNA-seq) was performed at a pre-symptomatic stage (10 months, n = 3/genotype). Differentially expressed genes (DEGs) were identified using pseudobulk DESeq2 and validated via immunofluorescence. Results: CLRN1-/- rabbits exhibited progressive outer nuclear layer thinning and delayed ERG responses starting after 20 months, mimicking human clinical kinetics. The snRNA-seq revealed that CLRN1 is exclusively expressed in a discrete subset (∼24%) of MG. Mutant MG exhibited transcriptomic downregulation of the adherens junction component CTNNA2, which was validated at the protein level by immunofluorescence staining. Photoreceptors exhibit extensive non-cell-autonomous dysregulation (232 rod and 68 cone DEGs) characterized by loss of the cone synaptic organizer TENM2 and rod-specific splicing dysregulation (CWF19L2). Concurrently, inner retinal neurons mounted a robust proteostatic response via HSP90 family upregulation (HSP90AB1, HSP90AA1, HSP90B1), a defensive signature absent in vulnerable photoreceptors. Conclusions: Our findings suggest an "anchor-shield" mechanism: MG CLRN1 loss compromises the outer limiting membrane (OLM) adhesion complex ("anchor"), and photoreceptors lack the proteostatic response ("shield") seen in resilient inner neurons. Restoring CLRN1 in Müller glia or implementing photoreceptor neuroprotection represents promising therapeutic strategies for USH3A.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.