Interleukin-1β and mitochondria damage, and the development of diabetic retinopathy

Abstract

Mitochondrial dysfunction is considered to play an important role in the development of diabetic retinopathy. Recent evidence has also shown many similarities between diabetic retinopathy and a low grade chronic inflammatory disease. The aim of this study is to understand the interrelationship between proinflammtory mediator, IL-1β and mitochondrial dysfunction in the accelerated loss of capillary cells in the retina. Using IL-1β receptor gene knockout (IL-1R1 − / − ) diabetic mice, we have investigated the effect of regulation of IL-1β on mitochondrial dysfunction and mtDNA damage, and increased retinal capillary cell apoptosis and the development of retinopathy. Retinal mitochondrial dysfunction and mtDNA damage were significantly ameliorated in IL-1R1 − / − mice, diabetic for~10 months, compared to the wild-type diabetic mice. This was accompanied by protection of accelerated capillary cell apoptosis and the development of acellular capillaries, histopathology associated with diabetic retinopathy. Thus, mitochondrial damage could be one of the key events via which increased inflammation contributes to the activation of the apoptotic machinery resulting in the development of diabetic retinopathy, and the possible mechanism via which inflammation contributes to the development of diabetic retinopathy includes continuous fueling of the vicious cycle of mitochondrial damage, which could be disrupted by inhibitors of inflammatory mediators.

Regulation of Retinal Inflammation by Rhythmic Expression of MiR-146a in Diabetic Retina

“…13 Immune function and inflammatory activity has been shown to be associated with circadian rhythm, with the peak of inflammatory activity occurring during the beginning of the sleep cycle. 49 Numerous studies demonstrated critical involvement of IL-1b in the pathogenesis of DR. 50,51 Indeed, IL-1b concentration is increased in diabetic retina. 34 Furthermore, blocking IL-1b production or signaling was shown to prevent vascular damage in the DR animal model.…”

Vitamin D3 Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS/TXNIP/NLRP3 Inflammasome Pathway

“…The ratio of proapoptotic Bax to antiapoptotic Bcl-2 in the retina reflects the level of retinal cell apoptosis in diabetic rats [ 31 ]. A previous study found that IL-1 β induced retinal mitochondrial dysfunction, mitochondrial DNA damage, and cell apoptosis [ 32 ]. Bax is a marker of mitochondrial stress associated with vascular diabetes complications [ 33 ].…”

Modulation of three key innate immune pathways for the most common retinal degenerative diseases

“…IL‐1β is a key inflammatory cytokine regulated by the inflammasome, and increased levels of IL‐1β are present in DR (Kowluru et al, ; Liu et al, ) and AMD (Lavalette et al, ; Tarallo et al, ). Amelioration of IL‐1β activation prevents mitochondrial dysfunction and DNA damage (Kowluru et al, ). Furthermore, glucose‐induced apoptosis of retinal endothelial cells is prevented by neutralization of IL‐1β through incubating the cells with an IL‐1β antibody or IL‐1β receptor antagonist (Kowluru & Odenbach, ).…”