Nitazoxanide reduced inflammatory markers and mitochondrial changes in human retinal endothelial cells grown in high glucose

Purpose To determine whether nitazoxanide (NΖT) can increase mitochondrial nuclear retrograde regulator 1 (MNRR1) in retinal endothelial cells (RECs) grown in normal or high glucose and thereby reduce inflammation. Methods We used control and diabetic human retinal protein samples, control and diabetic mouse retinal samples, and RECs grown in normal (5 mM) and high (25 mM) glucose protein samples to explore levels of MNRR1, high mobility group box 1, interleukin 1β, tumor necrosis factor α, and Tom20 by western blotting. We used immunostaining to localize MNRR1 in the retina. We also used a Seahorse XFe24 Bioanalyzer to measure the oxygen consumption rate in RECs under different conditions. Some cells were treated with NΖT to increase MNRR1 levels. Results MNRR1 protein levels were reduced in the diabetic retina of both humans and mice. MNRR1 was localized to RECs. RECs grown in normal or high glucose and treated with NΖT had significantly higher MNRR1 levels. NΖT reduced inflammatory markers in RECs grown in high glucose. NΖT increased the oxygen consumption rate in RECs grown in high glucose, which was associated with an increase in Tom20. Conclusions MNRR1 is reduced in the diabetic retina. NΖT increased MNRR1 levels in RECs. NΖT protected RECs grown in high glucose by reducing inflammatory mediators and mitochondrial dysfunction and increasing mitochondrial mass. NΖT may offer a new therapeutic option for diabetic retinopathy.