Improved Leukocyte Tracking in Mouse Retinal and Choroidal Circulation

Xu, Heping; Manivannan, A.; Goatman, Keith A; Liversidge, Janet; Sharp, P.; Forrester, John V.; Crane, Isabel J.

doi:10.1006/exer.2001.1134

Cited by 46 publications

(55 citation statements)

References 13 publications

(18 reference statements)

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“…102 Given that the eye is also uniquely placed as a window on the immune response, we will be able to harness and translate developments in ocular imaging, alongside immunophenotyping, to inform both basic understanding of intraocular inflammation and also a personalised readout of response to therapy in terms of immune cell trafficking, and such strategies have already been successfully applied in mice. 121 As the translational divide continues to be bridged there is real potential and optimism using the platforms discussed to revolutionise our understanding of immunity in general and, more specifically, deliver personalised care for patients with intraocular inflammatory diseases.…”

Section: Personalised and Stratified Medicinementioning

confidence: 99%

Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation

Lee

Dick

2011

Eye

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The blockbuster drug paradigm is under increasing scrutiny across the biopharmaceutical industry. Intraocular inflammation poses particular challenges to this, given the heterogeneity of conditions in the uveitis spectrum, and the increasing acknowledgement of individual patient and disease variance in underlying immune responses. This need has triggered a drive towards personalised and stratified medicine, supported and enabled as a result of continued development of both experimental models and molecular biological techniques and improved clinical classification. As such we have the ability now to systematically appraise at a genomic, transcriptomic, and proteomic level individual immunophenotype, and the promise that in the eye this can be augmented by in vivo immune imaging to identify individual immunopathology. With such advances all running in parallel, we are entering an era of experimental medicine that will facilitate early diagnosis, generate biomarkers for accurate prognostication, and enable the development of individualised and targeted therapies, which can progress rapidly into clinical practice.

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Section: Personalised and Stratified Medicinementioning

confidence: 99%

Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation

Lee

Dick

2011

Eye

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“…Scanning laser ophthalmoscopy. The technique of SLO in mice has been described in detail elsewhere (30,46). In brief, mice were anesthetized with an i.m.…”

Section: In Vivo Leukocyte Trafficking Assaymentioning

confidence: 99%

“…Fifty microliters of 0.05% (v/v) sodium fluorescein (Sigma-Aldrich) was injected via the tail vein to outline the vessels, followed by 1 ϫ 10 7 fluorescently labeled polarized cells, either untreated or Ab treated, in 150 l of complete medium. SLO images were recorded simultaneously on videotape (S-VHS) and digitally at 25 frames per second as described previously (46). For each eye, three regions of interest containing one to three veins/ venules were recorded for at least 30 min.…”

Section: In Vivo Leukocyte Trafficking Assaymentioning

confidence: 99%

“…The sticking efficiency was determined as the percentage of labeled leukocytes becoming firmly adherent for at least 20 s, compared with the total number of labeled leukocytes that rolled in a venule during the same time interval. Rolling velocities of 40 randomly chosen, rolling, labeled cells in retinal venules were measured in digital images (46). Leukocyte infiltration.…”

Section: In Vivo Leukocyte Trafficking Assaymentioning

confidence: 99%

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Recruitment of IFN-γ-Producing (Th1-Like) Cells into the Inflamed Retina In Vivo Is Preferentially Regulated by P-Selectin Glycoprotein Ligand 1:P/E-Selectin Interactions

Manivannan

Jiang

et al. 2004

The Journal of Immunology

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Although there is evidence that altering the Th1/Th2 balance toward Th2 cells may be important in the resolution of Th1-type autoimmune disease, adoptive transfer of Th2 cells is not effective in protecting against Th1-type disease and may cause disease. Therefore, we examined the recruitment of Th1- and Th2-like cells into the retina in the murine autoimmune disease experimental autoimmune uveoretinitis. CD4 T cells were polarized in vitro to IFN-γ-producing Th1-like cells and non-IFN-γ-producing Th2-like cells, labeled, and adoptively transferred. Trafficking to the retina in vivo was evaluated by scanning laser ophthalmoscopy and infiltration by confocal microscopy. There were more rolling and adherent Th1-like cells and they rolled more slowly than did Th2-like cells. Th1-like cells were preferentially recruited into the retinal parenchyma at both initiation and resolution. Surface P-selectin glycoprotein ligand 1 (PSGL-1) and LFA-1 were up-regulated on both populations but were expressed at higher levels on Th1-like cells. Up-regulation of CD44 expression was higher on Th2-like cells. P-selectin, E-selectin, and ICAM-1 are up-regulated on postcapillary venules in the retina. Pretreatment of Th1-like cells with anti-PSGL-1 inhibited rolling and infiltration of Th1-like cells but not Th2-like cells, providing direct in vivo evidence for the inability of Th2 to respond to P/E-selectin despite increased expression of PSGL-1. Anti-LFA-1 pretreatment inhibited infiltration of both Th1- and Th2-like cells, but more so Th-1. We suggest that random trafficking of activated T cells (both Th1 and Th2) across the blood-retina barrier is mediated by CD44:CD44R and LFA-1:ICAM-1, whereas preferential recruitment of Th1 cells is mediated by PSGL-1:P/E-selectin.

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“…We have therefore examined the changes in hemodynamic factors and their relationship to leukocyte rolling, adherence, and infiltration in the retina as inflammation develops, using a noninvasive, in vivo leukocyte-tracking method, which uses scanning laser ophthalmoscopy (SLO). We initially developed this system in rats [13] and have adapted it more recently for mice [14,15]. Individual, labeled cells can be visualized in retinal vessels under physiological flow conditions, and the velocity of the leukocytes and shear stress can be accurately measured.…”

Section: Introductionmentioning

confidence: 99%

Reduction in shear stress, activation of the endothelium, and leukocyte priming are all required for leukocyte passage across the blood—retina barrier

Xu¹,

Manivannan

Goatman

et al. 2003

Journal of Leukocyte Biology

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The passage of leukocytes across the blood-retina barrier at the early stages of an inflammatory reaction is influenced by a complex series of interactions about which little is known. In particular, the relationship between hydrodynamic factors, such as shear stress and leukocyte velocity, to the adherence and subsequent extravasation of leukocytes into the retina is unclear. We have used a physiological method, scanning laser ophthalmoscopy, to track labeled leukocytes circulating in the retina, followed by confocal microscopy of retinal flatmounts to detect infiltrating cells at the early stage of experimental autoimmune uveitis. This has shown that retinal vessels are subjected to high shear stress under normal circumstances. During the inflammatory reaction, shear stress in retinal veins is reduced 24 h before leukocyte infiltration. This reduction is negatively correlated with leukocyte rolling and sticking in veins and postcapillary venules, the sites of leukocyte extravasation. Activation of vascular endothelial cells is also a prerequisite for leukocyte rolling and infiltration. In addition, antigen priming of leukocytes is influential at the early stage of inflammation, and this is seen clearly in the reduction in rolling velocity and adherence of the primed leukocytes in activated retinal venules, 9 days postimmunization.

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Improved Leukocyte Tracking in Mouse Retinal and Choroidal Circulation

Cited by 46 publications

References 13 publications

Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation

Current concepts and future directions in the pathogenesis and treatment of non-infectious intraocular inflammation

Recruitment of IFN-γ-Producing (Th1-Like) Cells into the Inflamed Retina In Vivo Is Preferentially Regulated by P-Selectin Glycoprotein Ligand 1:P/E-Selectin Interactions

Reduction in shear stress, activation of the endothelium, and leukocyte priming are all required for leukocyte passage across the blood—retina barrier

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