Imaging ocular immune responses by intravital microscopy

The eye offers excellent opportunities to observe cellular interactions in vivo. This applies especially to the immune response in which discrete events can be studied, including cell trafficking, transendothelial migration, adhesion, antigen presentation, and T cell activation. Intravital microscopy has allowed study of immune cell interactions in tissues such as the conjunctiva, the inflamed cornea, and the iris. Thus the realtime observation of presentation of antigen injected into the anterior chamber of the eye can be imaged using fluorescently labelled antigen and cells. Application of the scanning laser ophthalmoscope to the rat and mouse eye allows analysis of leukocyte-endothelial interactions in the retinal and choroidal circulations. These studies have provided important information on rolling and adhesion of leukocytes in real time in different microvascular beds that have not been manipulated in any way and has, for instance, provided quantitation to the effects of shear stress on leukocyte-endothelial adhesion. In addition, the model permits an accurate analysis of the timing of trafficking of T cells into the eye and the possibility of determining which cells, if any, may be responsible for antigen presentation in the tissues as opposed to the secondary lymphoid organs. Finally, these experimental methods are now being applied to the human eye and should prove valuable in determining the nature of tissue damage events in the eye as well as evaluating the response to treatments.