Abstract
BackgroundThe aim of the present study was to identify the proteomic differences among human lenses in different physiopathological states and to screen for susceptibility genes/proteins via proteogenomic characterization.MethodsThe total proteomes identified across the regenerative lens with secondary cataract (RLSC), congenital cataract (CC) and age-related cataract (ARC) groups were compared to those of normal lenses using isobaric tagging for relative and absolute protein quantification (iTRAQ). The up-regulated proteins between the groups were subjected to biological analysis. Whole exome sequencing (WES) was performed to detect genetic variations.ResultsThe most complete human lens proteome to date, which consisted of 1251 proteins, including 55.2% previously unreported proteins, was identified across the experimental groups. Bioinformatics functional annotation revealed the common involvement of cellular metabolic processes, immune responses and protein folding disturbances among the groups. RLSC-over-expressed proteins were characteristically enriched in the intracellular immunological signal transduction pathways. The CC groups featured biological processes relating to gene expression and vascular endothelial growth factor (VEGF) signaling transduction, whereas the molecular functions corresponding to external stress were specific to the ARC groups. Combined with WES, the proteogenomic characterization narrowed the list to 16 candidate causal molecules.ConclusionsThese findings revealed common final pathways with diverse upstream regulation of cataractogenesis in different physiopathological states. This proteogenomic characterization shows translational potential for detecting susceptibility genes/proteins in precision medicine.
Highlights
The aim of the present study was to identify the proteomic differences among human lenses in different physiopathological states and to screen for susceptibility genes/proteins via proteogenomic characterization
The most complete proteome identification of human lenses and comprehensive quantification of the distinguished expressed proteins in different physiopathological states In total, 1251 proteins were identified across all lens samples, based on the detected protein threshold set at p < 0.05
Compared to their abundance in the normal lens, the abundances of the 261, 202, and 177 proteins identified in the regenerative lens with secondary cataract (RLSC), CC and age-related cataract (ARC) groups, respectively, were significantly upregulated., and 80 proteins were found in the overlapping areas
Summary
The aim of the present study was to identify the proteomic differences among human lenses in different physiopathological states and to screen for susceptibility genes/proteins via proteogenomic characterization. The disruption of the normal quality or quantity of lens constitutional proteins leads to the opacification of the refractive structure, namely, cataracts, which are the leading cause of blindness worldwide [2]. Cataracts can be induced under a variety of physiopathological states, including Three cases still exhibited evident secondary opacification of the regenerative lenses more than 2 years after primary surgery. The unique regenerative lens with secondary cataract (RLSC) model has enable the identification of a novel proteome composition and the characterization of a novel molecular mechanism underlying the predisposition to cataractogenesis [7, 8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
