Diabetic retinopathy: Involved cells, biomarkers, and treatments

Abstract

Diabetic retinopathy (DR), a leading cause of vision loss and blindness worldwide, is caused by retinal neurovascular unit dysfunction, and its cellular pathology involves at least nine kinds of retinal cells, including photoreceptors, horizontal and bipolar cells, amacrine cells, retinal ganglion cells, glial cells (Müller cells, astrocytes, and microglia), endothelial cells, pericytes, and retinal pigment epithelial cells. Its mechanism is complicated and involves loss of cells, inflammatory factor production, neovascularization, and BRB impairment. However, the mechanism has not been completely elucidated. Drug treatment for DR has been gradually advancing recently. Research on potential drug targets relies upon clear information on pathogenesis and effective biomarkers. Therefore, we reviewed the recent literature on the cellular pathology and the diagnostic and prognostic biomarkers of DR in terms of blood, protein, and clinical and preclinical drug therapy (including synthesized molecules and natural molecules). This review may provide a theoretical basis for further DR research.

Keywords: biomarkers; cells; diabetic retinopathy; drug therapy; potential drug targets.

FIGURE 1

The structure of retina. The retina comprises at least 10 distinct layers, including eleven cell types involved in the progress of DR. The factors related to these cells, described in this review are shown. (ILM, internal limiting membranes; NFL, nerve fiber layer; GCL, ganglion cell layer; IPL, inner plexiform layer; INL, inner nuclear layer; OPL, outer plexiform layer; ONL, outer nuclear layer; ELM, external limiting membranes; OS, outer segments; PEL, pigment epithelium layer; iBRB, inner blood-retina barrier; oBRB, outer BRB; VEGF, vascular endothelial growth factor; VEGFR2, VEGF receptor 2; SDF1, stromal cell-derived factor 1; CYP1B1, cytochrome P450 1B1; GSK3, glucogen synthase kinase 3; Nrf2, nuclear factor erythroid 2-related factor; TRIB3, tribbles homolog 3; TRPC, transient receptor potential canonical; GABA, γ-aminobutyric acid; ROS, reactive oxygen species; Glut1, glucose transporter 1; CTRP3, C1q/TNF-related protein 3).