Relationship between Biochemical Pathways and Non-Coding RNAs Involved in the Progression of Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is a progressive blinding disease, which affects the vision and quality of life of patients, and it severely impacts the society. This complication, caused by abnormal glucose metabolism, leads to structural, functional, molecular, and biochemical abnormalities in the retina. Oxidative stress and inflammation also play pivotal roles in the pathogenic process of DR, leading to mitochondrial damage and a decrease in mitochondrial function. DR causes retinal degeneration in glial and neural cells, while the disappearance of pericytes in retinal blood vessels leads to alterations in vascular regulation and stability. Clinical changes include dilatation and blood flow changes in response to the decrease in retinal perfusion in retinal blood vessels, leading to vascular leakage, neovascularization, and neurodegeneration. The loss of vascular cells in the retina results in capillary occlusion and ischemia. Thus, DR is a highly complex disease with various biological factors, which contribute to its pathogenesis. The interplay between biochemical pathways and non-coding RNAs (ncRNAs) is essential for understanding the development and progression of DR. Abnormal expression of ncRNAs has been confirmed to promote the development of DR, suggesting that ncRNAs such as miRNAs, lncRNAs, and circRNAs have potential as diagnostic biomarkers and theranostic targets in DR. This review provides an overview of the interactions between abnormal biochemical pathways and dysregulated expression of ncRNAs under the influence of hyperglycemic environment in DR.

Keywords: biochemical pathways; biomarkers; diabetic retinopathy; ncRNAs; oxidative stress.

Figure 1

Diabetes-induced hexosamine pathway, leading to leukostasis and inflammation. UDP-GLcNAc: uridine diphosphate N-acetylglucosamine.

Figure 2

Diabetes-induced polyol pathway, leading to retinal neuropathy and neurodegeneration. NADPH: nicotinamide adenine dinucleotide phosphate; GSH: glutathione; ROS: reactive oxygen species.

Figure 3

Diabetes-induced protein kinase C pathway (PKC) and AGEs formation, leading to microvascular dysfunction of retina. AGEs: advanced glycation end products; DAG: diglyceride; ET-1: endothelin-1; IGF-1: insulin-like growth factor 1; IL-1/6/8: interleukin 1/6/8; PARP: poly-(ADP-ribose)-polymerase; TNFα: tumor necrosis factor-α; VEGF: vascular endothelial growth factor.

Figure 4

The main non-coding RNAs associated with the pathomechanism of DR.