Crosstalk between oxidative stress, inflammation, angiogenesis and apoptosis in diabetic macular edema

Aims/Purpose: To evaluate molecules involved in oxidative stress (OS), inflammation, angiogenesis, and apoptosis, and discern which of these are more implicated in diabetic retinopathy (DR) and diabetic macular edema (DME) by investigating the correlation between them in the plasma (PLS) and vitreous humour (VIT), and examining data obtained from ophthalmological examinations. Methods: Type 2 diabetic (T2DM) patients with DR/DME (DRG/DMEG n = 112) and non‐DM subjects as the surrogate controls (SCG n = 48) were selected. Blood samples were processed to determine the glycaemic and lipid profiles, C reactive protein, malondialdehyde (MDA), 4‐hydroxynonenal (4HNE), superoxide dismutase (SOD), catalase (CAT) levels and total antioxidant capacity (TAC). In addition, interleukin 6 (IL6), vascular endothelial growth factor (VEGF), and caspase 3 were assayed. The VIT samples were collected to measure the expression levels of all the above‐mentioned molecules. Results: Our findings support the presence of molecules involved in OS, inflammation, angiogenesis, and apoptosis in the PLS and VIT samples from T2DM. In PLS from DRG, there was a decrease in the antioxidant load and an increase in pro‐angiogenic molecules, but an increase in pro‐oxidants and a decline in antioxidants intravitreally. In PLS from DMEG, pro‐oxidants and pro‐inflammatory molecules were augmented and the antioxidant capacity diminished, but the pro‐oxidants increased, and antioxidants decreased intravitreally. Furthermore, we found a positive correlation between the PLS‐CAT and the VIT‐SOD levels in DRG, and a negative correlation between the PSD‐4HNE and the VIT‐TAC levels in DMEG. Conclusions: We conclude that hyperglycaemia induces anomalies in biochemical pathways with crosstalk between them; MDA, 4HNE, TAC, VEGF, and IL6 are promoters of the clinical manifestations of PDR and DME. The above molecules have been selected as biomarker candidates for distinguishing T2DM patients at risk of DR, DME and vision loss.