Abstract
Myopia is a major public health concern with increasing global prevalence and is the leading cause of vision loss and complications. The potential role of the cornea, a substantial component of refractive power and the protective fortress of the eye, has been underestimated in the development of myopia. Our study acquired corneal stroma tissues from myopic patients undergoing femtosecond laser-assisted small incision lenticule extraction (SMILE) surgery and investigated the differential expression of circulating proteins between subjects with low and high myopia by means of high-throughput proteomic approaches—the quantitative tandem mass tag (TMT) labeling method and parallel reaction monitoring (PRM) validation. Across all corneal stroma tissue samples, a total of 2,455 proteins were identified qualitatively and quantitatively, 103 of which were differentially expressed between those with low and high myopia. The differentially abundant proteins (DAPs) between the groups of stroma samples mostly demonstrated catalytic activity and molecular function regulator and transporter activity and participated in metabolic processes, biological regulation, response to stimulus, and so forth. Pathway enrichment showed that mineral absorption, ferroptosis, and HIF-1 signaling pathways were activated in the human myopic cornea. Furthermore, TMT analysis and PRM validation revealed that the expression of ferritin light chain (FTL, P02792) and ferritin heavy chain (FTH1, P02794) was negatively associated with myopia development, while the expression of serotransferrin (TF, P02787) was positively related to myopia status. Overall, our results indicated that subjects with low and high myopia could have different proteomic profiles or signatures in the cornea. These findings revealed disturbances in iron metabolism and corneal oxidative stress in the more myopic eyes. Iron metabolic proteins could serve as an essential modulator in the pathogenesis of myopia.
Highlights
Myopia, as a complex multifactorial disease, is a globally recognized epidemic and a common cause of vision impairment characterized by its increasing prevalence among younger generations and heterogeneity among regions and ethnicities (Holden et al, 2016)
Since this study aimed at a proteomic evaluation for low versus high myopia eyes, an individual eye was set as a target, rather than an individual subject, which meant both eyes could be selected from the same subject
Protein Selection and Parallel Reaction Monitoring Measurements After a thorough evaluation of the gene ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein–protein interaction (PPI) network analysis, we focused on the main GO terms “ferric iron binding” and “oxidizing metal irons” and the main KEGG pathways “mineral absorption” and “ferroptosis.” we further selected three ironand redox-related differentially abundant proteins (DAPs), including serotransferrin (TF, P02787), ferritin light chain (FTL, P02792), and ferritin heavy chain (FTH1, P02794) for validation studies using the parallel reaction monitoring (PRM) approach
Summary
As a complex multifactorial disease, is a globally recognized epidemic and a common cause of vision impairment characterized by its increasing prevalence among younger generations and heterogeneity among regions and ethnicities (Holden et al, 2016). The projected mechanisms for myopia are universally considered to be triggered by a combination of genetic susceptibility and environmental elements, among which metabolic factors are the most intricate, with little implications from the available evolutionary analyses (Morgan et al, 2012). Previous practices have attempted to address the impact of retinal defocus, which triggers the retina–choroid pathway, or hypoxia of the sclera, which would cause scleral collagen remodeling (Morgan et al, 2018). The associated mechanisms have been predominantly studied in animal models. Steeper corneas have been implicated in high amounts of form-deprived myopia in experimental animal models (Qiao-Grider et al, 2010). Highquality analyses conducted in regions with the highest prevalence of myopia could provide useful information using representative clinical ocular samples
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