Daily proteome variations highlight sustained metabolic activity in cone cells of Nrl knockout mice

Vision is a highly rhythmic function adapted to daily changes in light intensity. Rhythms disruption is known to compromise retinal health and visual function. This study investigates expression patterns of cone proteins over the 24-h daily cycle in order to understand the molecular bases of cone cyclic physiology. Cones were isolated by vibratome-sectioning from Nrl knockout mice at four time points across the 24-h LD (Light-Dark) cycle and protein extracts were quantified by label-free LC-MS/MS. The resulting protein data was then submitted to MetaCycle analysis to identify proteins with rhythmic expression patterns and associated functions. Cyclic profiles were further validated by SWATH-MS analysis. A total of 1208 proteins were identified. Rhythmic expression patterns were found for 319 proteins, categorized into four clusters based on intensity variation. SWATH-MS analysis validated the approach. Functional enrichment analysis revealed proteins critical for photoreceptor function, including those involved in phototransduction, oxidative phosphorylation, RNA processing, proteostasis, transport, synaptic function and cilia biogenesis. These findings provide a unique dataset of rhythmic cone proteins, potentially crucial for elucidating cone cell physiology and visual function. This knowledge can empower future research on preventing and treating vision impairment.