Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Inhibition of stromal cell–derived factor-1α/CXCR4 signaling restores the blood-retina barrier in pericyte-deficient mouse retinas
Keisuke Omori, … , Akiyoshi Uemura, Takahisa Murata
Keisuke Omori, … , Akiyoshi Uemura, Takahisa Murata
Published December 6, 2018
Citation Information: JCI Insight. 2018;3(23):e120706. https://doi.org/10.1172/jci.insight.120706.
View: Text | PDF
Research Article Inflammation Ophthalmology

Inhibition of stromal cell–derived factor-1α/CXCR4 signaling restores the blood-retina barrier in pericyte-deficient mouse retinas

  • Text
  • PDF
Abstract

In diabetic retinopathy (DR), pericyte dropout from capillary walls is believed to cause the breakdown of the blood-retina barrier (BRB), which subsequently leads to vision-threatening retinal edema. While various proinflammatory cytokines and chemokines are upregulated in eyes with DR, their distinct contributions to disease progression remain elusive. Here, we evaluated roles of stromal cell–derived factor-1α (SDF-1α) and its receptor CXCR4 in the BRB breakdown initiated by pericyte deficiency. After inhibition of pericyte recruitment to developing retinal vessels in neonatal mice, endothelial cells (ECs) upregulated the expression of SDF-1α. Administration of CXCR4 antagonists, or EC-specific disruption of the CXCR4 gene, similarly restored the BRB integrity, even in the absence of pericyte coverage. Furthermore, CXCR4 inhibition significantly decreased both the expression levels of proinflammatory genes (P < 0.05) and the infiltration of macrophages (P < 0.05) into pericyte-deficient retinas. Taken together, EC-derived SDF-1α induced by pericyte deficiency exacerbated inflammation through CXCR4 in an autocrine or paracrine manner and thereby induced macrophage infiltration and BRB breakdown. These findings suggest that the SDF-1α/CXCR4 signaling pathway may be a potential therapeutic target in DR.

Authors

Keisuke Omori, Nanae Nagata, Kaori Kurata, Yoko Fukushima, Erika Sekihachi, Nobutaka Fujii, Tomoko Namba-Hamano, Yoshitsugu Takabatake, Marcus Fruttiger, Takashi Nagasawa, Akiyoshi Uemura, Takahisa Murata

×

Figure 2

Endothelial CXCR4 deficiency ameliorated the disruption of BRB.

Options: View larger image (or click on image) Download as PowerPoint
Endothelial CXCR4 deficiency ameliorated the disruption of BRB.
(A) Repr...
(A) Representative images of retina immunostaining of isolectin B4 (red) on P8. Scale bar: 500 μm (top); 100 μm (bottom). (B) The effect of endothelial CXCR4 deficiency (Cre+) on PBS- or APB5-treated retinal radius and vessel diameter on P8 (n = 5–6). (C) Representative images of retina immunostaining of isolectin B4 (red) and fibrinogen (green) on P8. Scale bar: 100 μm. (D) The effect of endothelial CXCR4 deficiency (Cre+) on PBS- or APB5-treated retinal fibrinogen intensity on P8 (n = 5–6). (E) Representative images of retina immunostaining of isolectin B4 (red) and F4/80 (green) on P8. Scale bar: 100 μm. (F) The effect of endothelial CXCR4 deficiency (Cre+) on PBS- or APB5-treated retinal F4/80-positive cells on P8 (n = 5–6). Significantly different from the results in Cre– mice at *P < 0.05, significantly different from the results in Cre– mice.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts