Regarding the molecular pathogenesis of proliferative diabetic retinopathy (PDR), chemokine signaling and cytokine-cytokine receptor interactions have particular significance, according to findings published in BMC Ophthalmology. “Our findings provide insight into the molecular pathogenesis of DR, which may be of value for disease diagnosis and treatment,” the researchers explain.
Researchers conducted a study to identify immune-related genes involved in the progression of PDR. Analysis of the “GSE102485” dataset of neovascular membrane samples (NVMs) from type 1 and 2 diabetes mellitus (DR1, DR2) patients, which was downloaded from the Gene Expression Omnibus database, was performed. The researchers conducted functional enrichment analysis, protein-protein interaction network (PPI) construction, and module analysis of immune pathways in NVMs and controls via Gene Set Enrichment Analysis and Metascape.
The study found that, in the DR2 and DR1 groups, the significantly upregulated hallmark gene sets were involved in 5 immune pathways. The only gene sets not previously reported in the context of PDR molecular pathophysiology were CCR4, CXCR6, C3AR1, LPAR1, C5AR1, and P2RY14. All of the above were upregulated in retinal samples from experimental diabetes mouse models and human retinal microvascular endothelial cells (HRMECs) treated with high glucose (HG) by quantitative real time polymerase chain reaction (qRT-PCR), except for P2RY14.
The researchers highlighted the finding that the most significantly enriched pathways were implicated mainly in chemokine signaling and cytokine-cytokine receptor internations. In addition to the study’s additional results, they say, this information may be of clinical value, as DR is one of the most common microvascular complications of diabetes and causes of blindness in developed countries.
Study limitations include the limited number of neovascularization samples from patients with DR1 and the normal retina samples.
Gao Y, Xue M, Dai B, et al. Identification of immune associated potential molecular targets in proliferative diabetic retinopathy. BMC Ophthalmol. Published online January 19, 2023. doi:10.1186/s12886/s12886-023-02774-y