Abstract
The blood-retina barrier (BRB), which is disrupted in diabetic retinopathy (DR) and uveitis, is an important anatomical characteristic of the retina, regulating nutrient, waste, water, protein, and immune cell flux. The BRB is composed of endothelial cell tight junctions, pericytes, astrocyte end feet, a collagen basement membrane, and perivascular macrophages. Despite the importance of the BRB, retinal perivascular macrophage function remains unknown. We found that retinal perivascular macrophages resided on postcapillary venules in the superficial vascular plexus and expressed MHC class II. Using single-cell RNA-Seq, we found that perivascular macrophages expressed a prochemotactic transcriptome and identified platelet factor 4 (Pf4, also known as CXCL4) as a perivascular macrophage marker. We used Pf4Cre mice to specifically deplete perivascular macrophages. To model retinal inflammation, we performed intraocular CCL2 injections. Ly6C+ monocytes crossed the BRB proximal to perivascular macrophages. Depletion of perivascular macrophages severely hampered Ly6C+ monocyte infiltration. These data suggest that retinal perivascular macrophages orchestrate immune cell migration across the BRB, with implications for inflammatory ocular diseases including DR and uveitis.
| Original language | English (US) |
|---|---|
| Article number | e180904 |
| Journal | Journal of Clinical Investigation |
| Volume | 134 |
| Issue number | 20 |
| DOIs | |
| State | Published - Oct 15 2024 |
Funding
This study was supported by an Unrestricted Departmental Grant from Research to Prevent Blindness. JKS was supported by the NEI Ruth L. Kirschstein Individual Predoctoral NRSA Fellowship F30 EY032339. JAL was supported by NIH grants K08 EY030923 and R01 EY034486 and by the Research to Prevent Blindness Sybil B. Harrington Career Development Award for Macular Degeneration. Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by CCSG P30 CA060553, awarded to the Robert H Lurie Comprehensive Cancer Center. Flow cytometry was performed at the Northwestern University \u2013 Flow Cytometry Core Facility supported by a Cancer Center Support Grant (National Cancer Institute [NCI], NIH CA060553). No funding body had any role in the design of the study, collection, analysis, interpretation of data, or in the writing of the manuscript. JAL received research grant support from Therini Bio. No company body had any role in the design of the study, collection, analysis, interpretation of data, or in the writing of the manuscript.
ASJC Scopus subject areas
- General Medicine
