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 real-time 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.

[1]  Erik Svensjö.  The hamster cheek pouch as a model in microcirculation research. , 1990, The European respiratory journal. Supplement.

[2]  R. Renkonen,et al.  A novel non-invasive, in vivo technique for the quantification of leukocyte rolling and extravasation at sites of inflammation in human patients , 2001, Nature Medicine.

[3]  P Hansell,et al.  L-selectin function is required for beta 2-integrin-mediated neutrophil adhesion at physiological shear rates in vivo. , 1992, The American journal of physiology.

[4]  U. Pleyer,et al.  In vivo study of leukocyte-endothelium interaction in endotoxin-induced uveitis. , 1995, Investigative ophthalmology & visual science.

[5]  Justine R. Smith,et al.  Anti-rat ICAM-1 antibody does not influence the course of experimental melanin-induced uveitis , 2000, Current eye research.

[6]  J. Kieffer,et al.  Interaction of Dendritic Cells with Skin Endothelium: A New Perspective on Immunosurveillance , 1999, Journal of Experimental Medicine.

[7]  P Massin,et al.  Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans. , 2000, Current eye research.

[8]  R. Caspi,et al.  Uveitogenic T lymphocytes in the rat: pathogenicity vs. lymphokine production, adhesion molecules and surface antigen expression , 1994, Journal of Neuroimmunology.

[9]  D F Chang.  Factoring cost, is phacoemulsification still the procedure of choice? , 2001, The British journal of ophthalmology.

[10]  G. Adamus,et al.  Myelin basic protein specific T‐helper cells induce experimental anterior uveitis , 1996, Journal of neuroscience research.

[11]  G. Lutty,et al.  T cell traffic and the inflammatory response in experimental autoimmune uveoretinitis. , 1998, Investigative ophthalmology & visual science.

[12]  M. Paques,et al.  Evaluation of fluorescein-labeled autologous leukocytes for examination of retinal circulation in humans , 2000 .

[13]  P F Sharp,et al.  Clinical investigation of a true color scanning laser ophthalmoscope. , 2001, Archives of ophthalmology.

[14]  H. Lassmann,et al.  Migratory activity and functional changes of green fluorescent effector cells before and during experimental autoimmune encephalomyelitis. , 2001, Immunity.

[15]  U. V. von Andrian.  Intravital microscopy of the peripheral lymph node microcirculation in mice. , 1996, Microcirculation.

[16]  H. Wekerle,et al.  Gene transfer into CD4+ T lymphocytes: Green fluorescent protein-engineered, encephalitogenic T cells illuminate brain autoimmune responses , 1999, Nature Medicine.

[17]  C. Chan,et al.  Endotoxin induced uveitis in the mouse: susceptibility and genetic control. , 1995, Experimental eye research.

[18]  J. Forrester,et al.  Immunopathogenic mechanisms in intraocular inflammation. , 1999, Chemical immunology.

[19]  Endogenous IL-12 is required for induction and expression of experimental autoimmune uveitis. , 1998, Journal of immunology.

[20]  Intraocular in vivo imaging of activated T-lymphocytes expressing green-fluorescent protein after stimulation with endotoxin , 2001, Graefe's Archive for Clinical and Experimental Ophthalmology.

[21]  F. Granucci,et al.  Analysis of the relationship between viral infection and autoimmune disease. , 2001, Immunity.

[22]  Chi-Chao Chan,et al.  Recruitment of antigen-nonspecific cells plays a pivotal role in the pathogenesis of a T cell-mediated organ-specific autoimmune uveoretinitis , 1993, Journal of Neuroimmunology.

[23]  M. Siemionow,et al.  In vivo microscopic assessment of cremasteric microcirculation during hindlimb allograft rejection in rats. , 1999, Plastic and reconstructive surgery.

[24]  H. Mcdevitt,et al.  Endotoxin-induced uveitis in rats as a model for human disease , 1980, Nature.

[25]  J. Rosenbaum,et al.  Reduced leukocyte migration, but normal rolling and arrest, in interleukin-8 receptor homologue knockout mice. , 2000, Investigative ophthalmology & visual science.

[26]  C. Chan,et al.  The requirement for pertussis to induce EAU is strain-dependent: B10.RIII, but not B10.A mice, develop EAU and Th1 responses to IRBP without pertussis treatment. , 1999, Investigative ophthalmology & visual science.

[27]  H. Lassmann,et al.  Apoptosis in brain-specific autoimmune disease , 1995, Current Opinion in Immunology.

[28]  Y. Ogura,et al.  Inhibitory effects of antithrombin III against leukocyte rolling and infiltration during endotoxin-induced uveitis in rats. , 2001, Investigative ophthalmology & visual science.

[29]  I. Mazo,et al.  Adhesion and homing of blood‐borne cells in bone marrow microvessels , 1999, Journal of leukocyte biology.

[30]  Y. Ogura,et al.  Retinal leukocyte behavior in experimental autoimmune uveoretinitis of rats. , 1997, Experimental eye research.

[31]  Janet Liversidge,et al.  Improved leukocyte tracking in mouse retinal and choroidal circulation. , 2002, Experimental eye research.

[32]  K. Suzuma,et al.  In vivo neutralization of P-selectin inhibits leukocyte-endothelial interactions in retinal microcirculation during ocular inflammation. , 1998, Microvascular research.

[33]  M. Stanford,et al.  Leukocyte trafficking in experimental autoimmune uveitis in vivo , 1998, Journal of leukocyte biology.

[34]  J. Rosenbaum,et al.  Digital video-imaging of leukocyte migration in the iris: intravital microscopy in a physiological model during the onset of endotoxin-induced uveitis. , 2000, Journal of immunological methods.

[35]  K. Wucherpfennig,et al.  In Vivo Survival of  Viral Antigen–specific T Cells that Induce Experimental Autoimmune Encephalomyelitis , 1998, The Journal of experimental medicine.

[36]  I. Gery,et al.  Autoimmunity in the eye and its regulation. , 1994, Current opinion in immunology.

[37]  C. Chan,et al.  Identification of a new epitope of human IRBP that induces autoimmune uveoretinitis in mice of the H-2b haplotype. , 2000, Investigative ophthalmology & visual science.

[38]  L. Donoso,et al.  Identification of a major pathogenic epitope in the human IRBP molecule recognized by mice of the H-2r haplotype. , 1995, Investigative ophthalmology & visual science.

[39]  J. Mizuguchi,et al.  Peptide-mediated suppression of experimental autoimmune uveoretinitis in mice: development of a peptide vaccine. , 1996, International immunology.

[40]  P F Sharp,et al.  In vivo cell tracking by scanning laser ophthalmoscopy: quantification of leukocyte kinetics. , 1998, Investigative ophthalmology & visual science.