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

Yan Wang; Xiongyi Yang; Qiumo Li; Yuxi Zhang; Lin Chen; Libing Hong; Zhuohang Xie; Siyu Yang; Xiaoqing Deng; Mingzhe Cao; Guoguo Yi; Min Fu

doi:10.3389/fnmol.2022.1048634

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

Front Mol Neurosci. 2022 Dec 1:15:1048634. doi: 10.3389/fnmol.2022.1048634. eCollection 2022.

Authors

Yan Wang¹, Xiongyi Yang², Qiumo Li², Yuxi Zhang², Lin Chen³, Libing Hong², Zhuohang Xie², Siyu Yang⁴, Xiaoqing Deng², Mingzhe Cao⁴, Guoguo Yi⁵, Min Fu⁶

Affiliations

¹ Department of Ophthalmology, South China Hospital of Shenzhen University, Shenzhen, China.
² The Second Clinical School, Southern Medical University, Guangzhou, Guangdong, China.
³ Department of Anesthesiology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.
⁴ Department of Ophthalmology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China.
⁵ Department of Ophthalmology, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
⁶ Department of Ophthalmology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.

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.

Keywords: Müller cell; blood–retinal barrier; communication network; diabetic retinopathy; single-cell RNA sequencing.