A single cell atlas of circulating immune cells involved in diabetic retinopathy

Area of Science:

• Immunology
• Ophthalmology
• Genetics

Background:

• Diabetic retinopathy (DR) is a significant complication of diabetes, leading to vision loss.
• The precise role of circulating immune cells in DR pathogenesis remains incompletely understood.
• Peripheral blood mononuclear cells (PBMCs) are key immune components potentially involved in DR.

Purpose of the Study:

• To elucidate the specific role of circulating immune cells in the development of diabetic retinopathy (DR).
• To identify molecular mechanisms by which PBMCs from DR patients affect retinal microvascular endothelial cells (HRMECs).
• To investigate the transcriptomic differences in circulating immune cells across healthy, non-DR, and DR patient groups.

Main Methods:

• In vitro co-culture experiments using PBMCs from type 1 DR patients and human retinal microvascular endothelial cells (HRMECs).
• Single-cell RNA sequencing (scRNA-seq) to analyze gene expression profiles in circulating immune cells.
• Gene manipulation (downregulation of JUND) in PBMCs to assess its impact on HRMEC function.

Main Results:

• PBMCs from type 1 DR patients impaired the normal function of HRMECs in co-culture experiments.
• scRNA-seq identified unique gene expression patterns in circulating immune cells of DR patients, with significant JUND upregulation observed across PBMC subsets.
• Downregulating JUND in DR patient-derived PBMCs ameliorated HRMEC dysfunction, indicating JUND's critical role.

Conclusions:

• Circulating immune cells, particularly PBMCs, exhibit distinct transcriptomic alterations in type 1 DR patients.
• The JUND gene is significantly upregulated in PBMCs from DR patients and plays a crucial role in DR pathogenesis.
• Targeting JUND in circulating immune cells may offer a therapeutic strategy for managing diabetic retinopathy.