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Published online before print November 21, 2003

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(Journal of Leukocyte Biology. 2004;75:224-232.)
© 2004 by Society for Leukocyte Biology

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

Heping Xu^*,1, Ayyakkannu Manivannan, Keith A. Goatman, Hui-Rong Jiang^*,2, Janet Liversidge^*, Peter F. Sharp, John V. Forrester^* and Isabel J. Crane^*,1

Departments of
^* Ophthalmology and
Biomedical Physics and Bioengineering, Aberdeen University Medical School, Scotland, United Kingdom

¹ Correspondence: Department of Ophthalmology, Aberdeen University Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK. E-mail: h.xu{at}abdn.ac.uk (H. X.) or i.j.crane{at}abdn.ac.uk (I. J. C.).

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.

Key Words: inflammation • leukocyte trafficking • blood flow • experimental autoimmune uveoretinitis • scanning laser ophthalmoscopy

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