Retinal Proteomic Alterations and Combined Transcriptomic-proteomic Analysis in the Early Stages Progression of a Mouse Model of X-Linked Retinoschisis

ABSTRACT: X-linked retinoschisis (XLRS) is among the most common inherited degenerative retinopathies. Functional impairment of RS1 protein is the cause of XLRS, which presents childhood onset with typical structural and functional alterations. However, the molecular mechanisms underlying RS1 malfunction remain largely uncharacterized. Here, we performed a data-independent acquisition (DIA)-mass spectrometry (MS)-based proteomic analysis in Rs1-null (Rs1-KO) mouse retina with different postal days (Ps), including the onset (P15) and early progression stage (P56). We compared the proteomic alternations in Rs1-KO mice at different stages to explore the underlying mechanisms during the disease progression. Compared with genotype, age showed a greater impact on retina proteomes. Gene set enrichment analysis (GSEA) showed that the regulation of type I interferon (IFN-I)-mediated signaling pathway was upregulated and photoreceptor proteins responsable for detection of light stimuli were downregulated at onset stage. Positive regulation of Tor signaling was downregulated and nuclear transcribed mRNA catabolic process (NTMCP) nonsense-mediated decay was upregulated at early progression stage. Moreover, the differentially expressed proteins (DEPs) at P15 were enriched in metabolism of RNA and RNA destabilization. Whereas at P56, a broader subcellular localization distribution and enriched proteins in visual perception and phototransduction were evident. Additionally, combined transcriptomic-proteomic analysis revealed 33 DEPs shared by the proteome at P56 and the reported transcriptome at P21. Enrichment analysis of the DEPs indicated that functional impairments including detection of visible light, visual perception, and visual phototransduction occurred at P21 and continued up to P56. Our work provided insights into the molecular mechanisms underlying the onset and progression of a XLRS mouse model in the early stage, which added further understanding towards the mechanims of XLRS.

ORGANISM(S): Mus Musculus

SUBMITTER: Bo Lei  

PROVIDER: PXD031901 | iProX | Sun Feb 27 00:00:00 GMT 2022

REPOSITORIES: iProX