Phosphocreatine protects against diabetic retinopathy via improving mitochondrial functions bioenergetics through JAK2/STAT3 signaling pathway in Vivo and in Vitro

Abstract The most prevalent chronic consequence of diabetes mellitus is diabetic retinopathy (DR), a clinically microvascular disease characterized by damage to retinal capillaries with subsequent visual deterioration or blindness. DR is mainly attributed to hyperglycemia-induced retinal microvascular damage, however, emerging research has demonstrated that it is intimately linked to mitochondrial energy shortage and raises the generation of reactive emerging research has demonstrated that it is intimately linked to mitochondrial energy shortage and raises the generation of reactive oxygen species (ROS). This study is aimed to develop and investigate methods to safeguard DR membrane composition, such as regaining methods to safeguard DR membrane composition, such as regaining mitochondrial function. Controlling for hyperglycemia cannot reverse the pathologic changes induced by diabetes in the retinal mitochondria. In mitochondria damaged by hyperglycemia, we proposed that phosphocreatine (PCr) might enhance oxidative phosphorylation and electron transport capability. Similarly, we anticipated estimating PCr's protection against DR via the JAK2/STAT3 signaling pathway. PCr has a crucial metabolic function in DR cells, which includes controlling the intracellular content of ATP. Rat mitochondria and RGC-5 cells were evaluated for capacity using high-resolution respirometry (HRR). The expression of JAK2/STAT3 signaling pathways and apoptotic proteins were detected using western blotting. We assessed ROS production and mitochondrial membrane potential (MMP) in Wistar male rats with streptozotocin induced-diabetes. In this study, we found that PCr had protective effects against DR injury by boosting mitochondrial bioenergetics and preventing DR by easing the symptoms of diabetes and improving biochemical indicators. Additionally, PCr decreased the expression of Bax, cleaved caspase 3, cleaved caspase 9, as well as the JAK2/STAT3 signaling pathway while increasing the expression of Bcl-2, caspase 3, and caspase 9 proteins. In Conclusions when exposed to oxidative stress caused by hyperglycemia, PCr improves mitochondrial activity and has antiapoptotic effects in vivo and in vitro through the JAK2/STAT3 signaling pathway. These findings suggest that PCr is a potentially effective therapeutic approach for diabetic retinopathy.