Cbr2, also known as NADH-Cytochrome B5 reductase 2, is involved in multiple biological processes. It has been implicated in angiogenesis and is related to the endocannabinoid system through cannabinoid receptor 2 (CBR2) [1,2,3,4,5,6,7]. In the context of the endocannabinoid system, CBR2 is expressed on leukocytes and plays a role in immunosuppression and inflammation regulation [5]. In addition, in non-primate species, Cbr2 is essential for sperm-zona pellucida interaction and fertilization [8].

In the study of diabetic retinopathy, Cbr2 expression was significantly downregulated in DM rat retinas and HG-stimulated human retinal microvascular endothelial cells (HRMECs). Intravitreal injection of CBR2-expressing lentivirus reduced retinal angiogenesis, acellular capillary formation, and pericyte loss, along with decreased expression of hypoxia-inducible factor-1α (HIF-1α), cluster of differentiation 31 (CD31), and vascular endothelial growth factor A (VEGFA) in vivo. CBR2 overexpression in HG-induced HRMECs inhibited cell growth and tube formation and decreased HIF-1α and VEGFA expression. When VEGFA was overexpressed, the repressive effects of CBR2 on cell proliferation, migration, and tube formation under HG conditions were reversed, suggesting Cbr2 alleviates retinal vascular dysfunction and abnormal endothelial proliferation by regulating VEGFA [1]. In breast cancer, nuclear CBR2 was negatively correlated with grade and positively correlated with estrogen receptor and progesterone receptor-positive status. High cytoplasmic expression of CBR2 was associated with a higher locoregional and distant recurrence rate, though not statistically significant [2]. In preterm birth, the expression of CBR2 in the placenta was significantly lower in women after preterm birth compared to those after term births, indicating that decreased CBR2 expression could potentially serve as an indicator for predicting preterm birth [6].

In conclusion, Cbr2 plays important roles in various biological processes and disease conditions. In diabetic retinopathy, it may regulate retinal vascular function by modulating VEGFA. In breast cancer, its expression is associated with certain prognostic factors. In preterm birth, its reduced placental expression might be a predictive marker. The study of Cbr2 through in vivo models such as in the diabetic retinopathy research helps to understand its function in disease mechanisms, providing potential targets for disease treatment.