The Proteome of mouse retinas harbouring CSNB2 variants

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 how variant-specific retinal proteome changes relate to disease severity. We developed an enrichment approach involving two centrifugation steps after cell lysis followed by in gel digest and analyzed by label-free proteomics. Proteomic analysis identified ~4000 proteins across wild-type and mutant retinas, revealing disruptions in synaptic remodeling, metabolism, postsynaptic organization, and calcium signaling for both variants. However, IT caused broader dysregulation than RX, including upregulation of stress response and apoptosis pathways and loss of vesicle-associated proteins.