Mechanisms of leukocyte migration across the blood-retina barrier
Open accessAbstract
Immune-mediated inflammation in the retina is regulated by a combination of anatomical, physiological and immuno-regulatory mechanisms, referred to as the blood-retina barrier (BRB). The BRB is thought to be part of the specialised ocular microenvironment that confers protection or "immune privilege" by deviating or suppressing destructive inflammation. The barrier between the blood circulation and the retina is maintained at two separate anatomical sites. These are the endothelial cells of the inner retinal vasculature and the retinal pigment epithelial cells on Bruch's membrane between the fenestrated choroidal vessels and the outer retina. The structure and regulation of the tight junctions forming the physical barrier are described. For leukocyte migration across the BRB to occur, changes are needed in both the leukocytes themselves and the cells forming the barrier. We review how the blood-retina barrier is compromised in various inflammatory diseases and discuss the mechanisms controlling leukocyte subset migration into the retina in uveoretinitis in more detail. In particular, we examine the relative roles of selectins and integrins in leukocyte interactions with the vascular endothelium and the pivotal role of chemokines in selective recruitment of leukocyte subsets, triggering adhesion, diapedesis and migration of inflammatory cells into the retinal tissue.
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These molecules promote leukocyte recruitment, adhesion, and infiltration through the blood-retinal barrier, resulting in breakdown of retinal immune privilege.
“These molecules function to promote leukocyte recruitment, adhesion, and infiltration through the blood-retinal barrier, ultimately resulting in a breakdown of retinal immune privilege.15,16”
From Characterizing the cellular immune response to subretinal AAV gene therapy in the murine retina (2021) · cites this paper as [16]
The Introduction describes the blood–retina barrier as part of retinal immune privilege, and the leukocyte-trafficking figure describes molecular signals that enable adhesion and infiltration and can lead to barrier breakdown. But the section ‘Mechanisms of blood–retina barrier breakdown in EAU’ says it is controversial whether infiltration causes barrier breakdown or follows it. The claimed outcome and causal sequence are therefore more definite than the paper supports. (LLM, conf=0.86)
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References 149 · Cited by 152
Research works printed but not linked: 1
- [84]Liversidge J Forrester JV Marmor MF Wolfensberger TJ Regulation of immune responses by the retinal pigment epithelium Retinal pigment epithelium, current aspects of function and disease 1999 Oxford Oxford University Press 511 527 Liversidge J, Forrester JV (1999) Regulation of immune responses by the retinal pigment epithelium. In: Marmor MF, Wolfensberger TJ (eds) Retinal pigment epithelium, current aspects of function and disease. Oxford University Press, Oxford, pp 511–527
- Authors
- Crane, I. J., & Liversidge, J.
- Affiliations
- University of Aberdeen (GB)
- Corresponding author
- Liversidge, Janet
- Venue
- Seminars in Immunopathology
- Published
- 2008-02-28
- Volume
- 30
- Issue
- 2
- Pages
- 165-177
- ISSN
- 1863-2297 (ISSN-L)
- 1863-2300
- PMC
- PMC2315689
- OpenAlex
- W1974615320
- Cited by
- 152
- References
- 149
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 16 · 2023: 7 · 2022: 10 · 2021: 15 · 2020: 10 · 2019: 7 · 2018: 4 · 2017: 6 · 2016: 6 · 2015: 6 · 2014: 4 · 2013: 7 · 2012: 15
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Seminars in Immunopathology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (068109)
- Topics
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- blood-retinal barrier, leukocyte migration, uveoretinitis, immune privilege, tight junctions, retinal pigment epithelium, choroidal vasculature, selectins, integrins, chemokines, leukocyte adhesion, transendothelial migration, retinal inflammation, ocular immune privilege
- MeSH terms
- Animals, Blood-Retinal Barrier, Chemotaxis, Leukocyte, Humans
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