Metabolic memory in mitochondrial oxidative damage triggers diabetic retinopathy.

BACKGROUND

Diabetic retinopathy (DR) is a microvascular complication induced by high blood glucose. This study was conducted to investigate the effect of metabolic memory on mitochondrial oxidative damage-induced DR.

METHODS

Rat retinal endothelial cells (rRECs) were isolated from SD rats and treated with high glucose (20 mM) for various times and then cultured in normal glucose (5.6 mM) medium for 2 days. The cells were assayed for the expression of respiratory chain complexes cytochrome c oxidase subunit 1 (CO1) and NADPH-1 using RT-PCR, mitochondrial membrane potentials and reactive oxygen species (ROS) production using flow cytometry and apoptosis using Annexin V/PI flow cytometry.

RESULTS

rRECs displayed like short spindles after cultured for 9-10 days and reached 100% confluency. Compared with the control grown in normal glucose (5.6 mM) medium, rRECs exposed to high glucose medium for 3, 12 and 24 h had significantly increased mRNA levels of CO1 and NAPDH-1 even after being shifted back to normal glucose medium. They also had lower mitochondrial membrane potential (89.13% vs 78.21%, p < 0.05), cytochrome C level (1 in control vs 0.25 after 24 h exposure to high glucose, p < 0.05 and higher ROS production (2.77% in control vs 9.00% after 12 h exposure to high glucose, p < 0.05) and apoptosis (7.15% in control vs and 29.91% after 24 h exposure to high glucose, p < 0.05).

CONCLUSION

It is likely that mitochondrial oxidative damage triggers metabolic memory via ROS overproduction, leading to diabetic retinopathy.