Abstract
Purpose :
Diabetic retinopathy (DR) is a serious complication associated with diabetes by increasing the risks of microvasculature abnormality, which results from uncontrollable metabolite-induced angiogenesis, which leads to vision impairment and eventual blindness if not treated. Although low levels of adiponectin are associated with microvasculature complications, its role in the pathogenesis of diabetic retinopathy remains unclear.This study investigated the role of adiponectin exposed to a hyperglycemic environment on human microvascular retinal endothelial cells (HMRECs) and essentially identifying its potential therapeutic use for DR.
Methods :
HMRECs cells were exposed to 30mM glucose and treated with various concentrations of adiponectin (5 and 30ug/ml) for 24 hours. The cells were evaluated for cellular events such as cell viability, oxidative stress (ROS) and apoptosis by image flowcytometry. Nitric oxide was assessed using a dye fort Reactive Nitrogen Species (RSN) measurements in HMRECs. The gene expression of adiponectin receptors (ADR1 and ADR2), and eNOS by real time PCR. The adhesion molecules E-selectin and ICAM-1 were evaluated by flowcytometery, and the barrier function was measured by real dynamic assay over 90 hours by the impedance analysis of Transelectrical resistance measurement using ECIS.
Results :
Hyperglycemia HMRECs demonstrated a significant increase in apoptosis and ROS production compared to normoglycemic HMRECs, which were significantly reduced after treatment with 30ug/ml adiponectin treatment. Adiponectin treatment in hyperglycemic cells significantly upregulated the AdipoR1 and reduced the expression of eNOS. Consistent with eNOS data, the (RNS) significantly increased in hyperglycemic cells followed by a significant reduction with adiponectin treatment. The E-selectin and ICAM-1 levels were significantly elevated in hyperglycemia and declined significantly after adiponectin. Lastly, the TRE in hyperglycemic cells is decreasing indicating barrier dysfunction but improved with adiponectin treatment.
Conclusions :
Adiponectin can significantly counteract the effects of hyperglycemia at various cellular and molecular levels, thereby reducing the impact of hyperglycemia on the pathophysiological progression towards DR.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.