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Updated: Jan 11, 2026
Mouse Eye Enucleation for Remote High-throughput Phenotyping
Published on: November 19, 2011
Quantitative Proteomics Identifies Potential Molecular Adaptations in Mouse Models of Congenital Stationary Night
Matthias Ganglberger1, Lucia Zanetti1, Anna-Sophia Egger2
1Institute of Pharmacy, Pharmacology and Toxicology Unit, University of Innsbruck, Innsbruck, Austria.
Abstract:
Pathogenic variants in the CACNA1F gene are linked to congenital stationary night blindness type 2 though their specific molecular effects remain elusive. This study examines the retinal impact of two variants: a truncation (RX) and a gain-of-function (IT) to explore variant-specific retinal proteome changes. Electroretinography showed that RX primarily affects rod pathways, while IT disrupts both rod and cone signaling, consistent with morphological findings. Comprehensive quantitative proteomic analysis using mass spectrometry identified approximately 4000 proteins across wild-type control and mutant retinas, including also low-abundant membrane proteins. IT retinas exhibited widespread proteomic remodeling suggesting broad cellular responses and also compensatory molecular adaptations. In contrast, RX retinas displayed a more restricted profile. Similar to IT retinas, we found reduced Cav1.4 protein levels but without transcriptional downregulation in RX, alongside selective changes in synaptic proteins such as Erc1, Lrfn2, vGlut1, and Rab3a. These findings suggest selective molecular changes in synaptic organization and calcium-related pathways in RX retinas, offering insights into the mechanisms of Cav1.4 dysfunction in retinal disease. Deep proteomic analysis demonstrates how retinal cells reorganize their molecular architecture in response to calcium channel defects and highlights the utility of comprehensive proteomics to characterize adaptive cellular responses to genetic perturbations in retinal synaptic organization.
Insights
Pathogenic CACNA1F gene variants cause night blindness. This study reveals distinct proteomic changes in retinas with truncation (RX) and gain-of-function (IT) variants, impacting rod and cone pathways.
Area of Science:
- Ophthalmology
- Genetics
- Molecular Biology
Background:
- Pathogenic variants in the CACNA1F gene are associated with congenital stationary night blindness type 2.
- The precise molecular mechanisms underlying CACNA1F-related retinal dysfunction are not fully understood.
Purpose of the Study:
- To investigate the variant-specific retinal proteome alterations caused by CACNA1F truncation (RX) and gain-of-function (IT) variants.
- To elucidate the molecular impact of these variants on retinal pathways and cellular responses.
Main Methods:
- Utilized electroretinography to assess retinal function in RX and IT variant models.
- Performed comprehensive quantitative proteomic analysis using mass spectrometry on wild-type and mutant retinas.
- Identified approximately 4000 proteins, including low-abundant membrane proteins.
Main Results:
- Electroretinography indicated RX variants primarily affect rod pathways, while IT variants disrupt both rod and cone signaling.
- Proteomic analysis revealed widespread remodeling in IT retinas, suggesting broad cellular and compensatory responses.
- RX retinas showed a more restricted proteomic profile with selective changes in synaptic proteins and reduced Cav1.4 levels without transcriptional downregulation.
Conclusions:
- CACNA1F variants induce distinct retinal proteomic changes, influencing synaptic organization and calcium-related pathways.
- The study highlights the adaptive molecular reorganization of retinal cells in response to calcium channel defects.
- Comprehensive proteomics is valuable for characterizing cellular adaptations to genetic perturbations in retinal synaptic function.
