Introduction 120 121 15 99 76 72 9 137 1 1 12 45 Fig. 1 1 2 3 4 5 Ve signal? Ve signal?  53 Leukocyte adhesion cascade Adhesion molecules in the leukocyte adhesion cascade 82 119 89 44 59 6 78 87 113 126 Chemokines in the leukocyte adhesion cascade 109 92 7 143 32 130 77 111 13 110 124 95 96 5 104 6 20 26 74 129 23 24 142 24 Normal retina and immune surveillance 15 99 Structure and function of the blood–retina barrier 53 1 4 132 134 1 46 102 33 90 98 46 63 Leukocyte infiltration of normal retina 135 137 103 139 65 66 5 138 68 101 103 Leukocyte infiltration of the retina during inflammation 21 88 11 14 46 Angiogenesis and inflammation 64 70 15 120 69 105 52 56 97 57 128 80 N l l Leukocyte infiltration of the retina in uveoretinitis 49 17 50 38 83 5 16 17 50 103 114 122 18 Mechanisms of leukocyte migration across the blood–retina barrier in uveoretinitis Adhesion molecules involved in leukocyte–endothelial cell interactions Appropriate adhesion molecule expression on both leukocytes and cells of the BRB is clearly important in enabling the migration of leukocytes into the inflamed retina. 108 85 58 61 94 37 79 40 93 60 19 67 84 Mechanisms of leukocyte subset migration into the retina 131 2 137 135 140 34 35 140 10 27 + 137 136 + + Mechanisms of blood–retina barrier breakdown in EAU 60 86 1 62 2 135 116 133 133 The role of chemokines in leukocyte migration across the BRB in EAU 91 111 36 71 115 8 107 109 22 111 28 28 31 51 51 51 29 41 42 51 30 30 31 127 39 39 117 136 136 106 112 123 −/− 112 125 125 55 25 81 47 118 55 123 Conclusions and implications for design of novel therapies Current treatment for uveitis is still dependent in the most part on systemic, non-specific immunosuppression. Additional therapies such as cyclosporin A, tacrolimus and rapamycin may act by interfering with the production and action of cytokines, particularly interleukin-2, targeting T cell function. Mycophenolate mofetil, an antimetabolite affecting purine synthesis, is also valuable. Other immunosuppressants such as azathioprine, cyclophosphamide and chlorambucil have severe side effects restricting their use. Blockade of TNF-α is also effective at least in the short term and now used clinically in different forms. Despite the usefulness of these therapies, they are all relatively non-specific, and in recent years, the quest for specific, tailored therapies for uveitis has been paramount. 3 54 100 141 73 75 48 43