Abstract
Purpose :
Diabetic retinopathy (DR) is a common complication of diabetes that leads to progressive vision loss. Although hyperglycemia (HG) plays an important role in its pathogenesis, a growing body of evidence suggests that pro-inflammatory conditions in the eye enhance DR development and progression. In this study, we investigated the combined effect of HG and inflammation on the early stages of disease by assessing retinal function and metabolic homeostasis.
Methods :
HG was induced in C57Bl/6 mice within one week of administering a single intraperitoneal injection of streptozotocin (150 mg/kg), while control mice received a sham injection. After confirming HG, mice received an intravitreal injection (IVT) of 500 ng/ml of each pro-inflammatory cytokine TNF-α and IL-1β (HG+cytokines group, n=6) or a sham injection (HG-only group, n=6). Control mice received an IVT of pro-inflammatory cytokines (cytokines-only group, n=6) or a sham injection (control group, n=6). The retinal function (focal electroretinogram on the superior retina) was evaluated two days after IVT and the retina was immediately collected for biochemical analysis to determine retinal glucose, lactate, ATP, glutamate and glutamine levels.
Results :
A similar significant decrease in the a-wave amplitude was observed in both HG-only and HG+cytokines groups at higher light intensities 2.6 and 3.2 log cd.s/m2 (p<0.01) compared with control. A significant decrease in the b-wave amplitude was observed in the HG-only group at 2.6 log cd.s/m2 (p<0.05) and it was significantly further decreased in the HG+cytokines group at the higher light intensities 2, 2.6 and 3.2 log cd.s/m2 (p<0.05).While the HG-only group showed elevated glucose levels (p<0.01), the HG+cytokines group showed a significantly higher retinal glucose (p<0.001), lactate (p<0.001), ATP (p<0.001), glutamine (p<0.05) levels, and a significant decrease in glutamate (p<0.05) levels compared with control. The cytokines-only group showed no significant changes compared with control.
Conclusions :
The presence of pro-inflammatory cytokines in the eyes of HG mice altered the retinal metabolic homeostasis and retinal function in the photopic range. These findings support the idea that combined presence of HG and inflammation may enhance DR development. Hence, early intervention to prevent inflammation-triggered retinal changes in diabetic patients may improve the disease outcome.
This is a 2021 ARVO Annual Meeting abstract.