Single-cell RNA sequencing reveals the Müller subtypes and inner blood-retinal barrier regulatory network in early diabetic retinopathy.

ABSTRACT

As the basic pathological changes of diabetic retinopathy (DR), the destruction of the blood-retina barrier (BRB) and vascular leakage have attracted extensive attention. Without timely intervention, BRB damage will eventually lead to serious visual impairment. However, due to the delicate structure and complex function of the BRB, the mechanism underlying damage to the BRB in DR has not been fully clarified. Here, we used single-cell RNA sequencing (RNA-seq) technology to analyze 35,910 cells from the retina of healthy and streptozotocin (STZ)-induced diabetic rats, focusing on the degeneration of the main cells constituting the rat BRB in DR and the new definition of two subpopulations of Müller cells at the cell level, Ctxn3 +Müller and Ctxn3 -Müller cells. We analyzed the characteristics and significant differences between the two groups of Müller cells and emphasized the importance of the Ctxn3 +Müller subgroup in diseases. In endothelial cells, we found possible mechanisms of self-protection and adhesion and recruitment to pericytes. In addition, we constructed a communication network between endothelial cells, pericytes, and Müller subsets and clarified the complex regulatory relationship between cells. In summary, we constructed an atlas of the iBRB in the early stage of DR and elucidate the degeneration of its constituent cells and Müller cells and the regulatory relationship between them, providing a series of potential targets for the early treatment of DR.