Identification of potential biomarkers of myopia based on machine learning algorithms

There is growing evidence confirming that myopia is not simply a refractive error, but is influenced by many factors [13]. In this study, we compared the gene expression profiles of myopic patients’ corneas to those from normal populations. We searched both datasets for differentially expressed genes, and then we merged the results to uncover co-regulated genes. This analysis revealed 23 co-regulated genes to be myopia-related differentially expressed genes. The generation of carbohydrates is primarily impacted by the 23 distinct genes indicated above, which are involved in polysaccharide biosynthesis. High glucose levels may impact the glycosylation of corneal fibers and collagen cross-links in the corneal stroma, limiting the biomechanical weakening of the cornea and lowering the occurrence of conical corneas, according to earlier research [14, 15], while the body’s blood glucose levels can be influenced by the processes of carbohydrate synthesis and polysaccharide synthesis, which are enriched by separate genes, which is consistent with earlier research. Subsequent machine-learning analysis revealed four genes—NR1D1, PPP1R18, PGBD2, and PPP1R3D—as potential myopia biomarkers, all demonstrating robust diagnostic efficiency.The single gene GSEA results for the aforementioned four genes reveal that each of these four genes has an impact on the pathway for ubiquitin-mediated protein hydrolysis. All eukaryotic cells contain ubiquitin, which alters proteins for proteasomal breakdown and non-protein hydrolysis processes [16]. The ubiquitin protein hydrolysis system plays important role in the cell. These include regulation of the cell cycle, regulation of immune and inflammatory responses, control of signal transduction pathways, development, and differentiation [17]. These complex processes are controlled by the specific degradation of a protein or group of proteins. The role of ubiquitination in ophthalmology has been studied in several ways. In a study by Fu SH et al. [18], the epithelial-mesenchymal transition and cell permeability of retinal pigment epithelial cells were discovered to be impacted by the ubiquitination degradation process, which has an impact on diabetic retinopathy. In a study by Annika N Boehm et al. [19], it was discovered that in inflammatory eye diseases, the human leukocyte antigen (HLA)-F adjacent transcript 10 (FAT10) family of ubiquitin-like modifiers can lead to the loss of phosphodiesterase 6 (PDE6) by targeting PDE6 for proteasomal degradation through the formation of covalent covalent bonds. All of the myopia-related biomarkers examined in this investigation alter ubiquitin-mediated protein hydrolysis, but more research is required to determine the precise role of ubiquitin-mediated protein hydrolysis in the onset and progression of myopia.

NR1D1 is involved in metabolism, autophagy, cell proliferation, inflammation and other processes and regulates a variety of diseases [20‐22]. It is not only a regulator of circadian clock metabolism, but also an important nuclear receptor for the normal function of mammalian retina [23]. Importantly, it can also regulate the expression of many genes in the retina [24, 25]. Studies have confirmed that NR1D1 reverses the functional NR2E3 gene in retinal degeneration mice. Therefore, NR1D1 can be used as a new therapeutic drug for retinal degeneration [23]. Additionally, it was shown that NR1D1 reduced retinal inflammation and prevented the activation of microglia linked to the start of retinal inflammation [26]. Protein phosphatase 1(PP1) is a major serine/threonine phosphatase that is expressed in all eukaryotic cells [27]. Previous research has revealed that the PP1-binding proteins protein phosphatase 1 regulatory subunit 18 (PPP1R18) and PPPIR subunit 3D (PPP1R3D) play a critical role in regulating vertebrate studies of development [28]. In addition, PP1 plays a key role in both the lens and human retinal epithelium [29]. PGBD2 is a member of the PiggyBac family [30], and there are few studies on the relationship between PGBD2 and myopia. The value of this gene in myopia diagnosis identified in this study may inspire subsequent studies.

In the current study, we compared patients with different degrees of myopia to normal cornea patients, searching for differentially expressed genes, investigating the functions of these genes, identifying key myopia biomarkers, studying the diagnostic efficacy of these key biomarkers, and based on GSEA analysis, identifying several key pathways that may be involved in myopia progression. These findings have contributed to our understanding of the pathophysiology of myopia. However, due to the limited sample size in this study, the strength of the evidence is reduced. We will use this research as a stepping stone for more clinical and basic experimental studies to further validate our findings, as the exact mechanisms of myopia are still largely unknown.

To further understand the potential roles of these genes in high myopia, future research should consider using larger sample populations and including more patients with high myopia. We will also explore whether these genes are associated with high myopia. Additionally, we plan to further investigate how these genes influence cellular functions and how they may interact with environmental factors to affect the severity of myopia. Through such efforts, we hope to gain a better understanding of the genetic basis of high myopia and potentially guide future treatment strategies.