In the current study, we utilized three high-throughput sequencing datasets (GSE94019, GSE102485, and GSE191210) to screen genes involved in PDR and obtain key co-expression modules implicated in the pathogenesis of PDR. Through PPI network analysis and further functional enrichment analysis, four key genes involved in PDR were identified, including CACNA1A, CACNA1E, PDE1B, and CHRM3, which were enriched in the calcium signaling pathway. Of note, our PPI results using the STRING database demonstrated CACNA1A as the only key gene interacting with angiogenesis-related genes. The STRING database is used for PPI network aiming to integrate all known and predicted associations between proteins, including both physical interactions and functional associations.
26 In a single-cell transcriptome analysis of the Akimba mouse retina by Van et al., they studied DEG networks in neuronal, glial, and immune cell compartments using the STRING database.
27 Retinal and choroidal neovascularization are a leading cause of visual impairment worldwide. A previous study has retrieved a PPI network from 42 proteins (organism searched: Homo sapiens), available at version 10.0 of STRING (with a minimum required interaction score of 0.400) and concluded that the combination of blockades and/or enhancements of different molecules, to manage the complex angiogenesis-related PPI is probably the future treatment of retinal and choroidal neovascularization.
28 High-throughput techniques have witnessed rapid advancements, fueling the production of biological data on a large scale at affordable costs and inducing the exponential growth of the size of many biological databases, including National Center for Biotechnology Information (NCBI)-GEO.
29 Recent studies have used either the GSE94019 or GSE102485 datasets to identify key genes related to the hallmark processes of DR. For instance, by analyzing DEGs in GEO datasets (GSE60436 and GSE94019), three hub genes (COL1A1, COL1A2, and SERPINH1) have been demonstrated to be potentially associated with DR pathophysiology.
30 In a recent study, differential analysis of the GSE102485 dataset identifies CCN1 as an important regulator in the pathogenesis of DR.
31 Analysis of the dataset GSE94019 downloaded from the GEO database together with conjoint analysis using WGCNA and Cytoscape software obtains 3 hub genes, EEF1A1, RPL11, and RPS27A, and reveals their relationship to the pathogenesis of PDR.
32 In addition, following differential analysis of the GSE102485 dataset, 3 genes (FCGR3A, DPEP2, and ADGRF5) are upregulated in PDR samples and as potential biomarkers for PDR.
33 Lack of CACNA1A has also been unfolded in different disorders. For instance, CACNA1A displayed downregulated expression during epileptogenesis.
34 In addition, CACNA1A was unfolded as one of the crucial genes for insulin secretion in beta cells.
35 Moreover, CACNA1A can mediate the calcium signaling pathway
36 that participates in the development of diabetic retinal rod bipolar cells.
37