Effect of lymphocytic infiltration on the blood-retinal barrier in experimental autoimmune uveoretinitis.
Using an experimental model of autoimmune uveoretinitis, we have examined the relationship of T cell infiltration in the retina to blood-retinal barrier (BRB) breakdown. Sensitive quantitative in vivo techniques were used to examine BRB permeability to sucrose, a low mol. wt non-transported solute. Electron microscopy was also used to localize extravasated horseradish peroxidase, a macromolecular visual tracer, from the retinal vasculature and to identify the route by which any leakage was occurring. No increase in BRB permeability was found prior to lymphocytic infiltration. By day 10 of the disease inflammatory cells could be seen within the structurally intact retina, which was shortly followed by an increase in the permeability of the BRB to sucrose. Only later in the disease process, when damage to the photoreceptor layer became apparent, did extravasation of the macromolecule HRP occur. At no stage of the disease process was there any detectable damage to inter-endothelial tight junctions. The size-dependancy of tracer extravasation in the initial stages of the disease is indicative of a paracellular route being responsible for the increase in BRB permeability. In later stages of the disease some evidence of horseradish peroxidase filled 'vesicle-like' profiles was observed. We suggest that the devastating complication of BRB breakdown in ocular inflammation is a direct consequence of lymphocytic infiltration.
Lightman
S
S
Department of Clinical Science, Institute of Ophthalmology, London, UK.
Greenwood
J
J
D000818:Animals; D001813:Blood-Retinal Barrier / Q000502:physiology*; D002465:Cell Movement; D004195:Disease Models, Animal; D005260:Female; D006735:Horseradish Peroxidase / Q000493:pharmacokinetics; D008214:Lymphocytes / Q000502:physiology*; D008854:Microscopy, Electron; D010539:Permeability; D051381:Rats; D011917:Rats, Inbred Lew; D013395:Sucrose / Q000493:pharmacokinetics; D013997:Time Factors; D015866:Uveitis, Posterior / Q000473:pathology*
D013395:Sucrose; D006735:Horseradish Peroxidase