The Novel Aryl Hydrocarbon Receptor Activator, Aza-PBHA, attenuated diabetes-induced capillary loss and inflammation of retina in type II diabetic mice.

抄録

Recent researches revealed that the global prevalence of diabetes mellitus is increasing. According to the International Diabetes Federation prevalence, there were 463 million diabetes mellitus patients in 2019 and will grow to 700 million in 2045. Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus that affects the retina and leads to visual disability and blindness . Aryl hydrocarbon receptor (AhR), a ligand-activated nuclear receptor, has been identified as an essential role in multiple aspects of normal physiology, including vascular development, neurologic function, inflammation, and vision. Aza-PBHA (AzP), an aryl hydrocarbon receptor activator, is a patented compound could inhibit human gastric cancer cell migration in in vitro study and decrease inflammation cytokine in the hamster oral mucositis model. This study was to estimate the treatment potential of AzP in DR. The results showed that AzP (500 mg/kg/day) oral treatment for 12 weeks attenuated the DR retinal changes in db/db mice such as reduced vascular density, retinal blood perfusion, retinal thickness and increased DR lesion, VEGF expression, and lipofuscin accumulation. In addition, AzP treatment reversed the high-glucose-induced AhR decrease and HIF-1α increase in ARPE-19 cells. We concluded, the AhR activator, AzP, is considered a potential candidate to inhibit the DR development.