SOLUBLE LEUKOCYTE ADHESION MOLECULES IN DIABETIC-RETINOPATHY STIMULATE RETINAL CAPILLARY ENDOTHELIAL-CELL MIGRATION

Diabetic retinal neovascularisation is considered to be a consequence of retinal ischaemia caused by capillary occlusion. Capillary occlusio n is the result of microvascular thrombi in which erythrocytes, platel ets and leucocytes each may play a role. We investigated the role of l eucocytes in this process and the subsequent angiogenic response. We s tudied the serum levels of the soluble leucocyte adhesion molecules so luble E-Selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) in the serum o f 93 patients with insulin-dependent diabetes (IDDM) and varying degre es of retinopathy and 47 healthy age and sex matched control subjects. We also measured the ability of serum to stimulate retinal capillary endothelial cell migration using an assay of angiogenesis in vitro. So luble E-Selectin and sVCAM-1 levels were raised in all patients with I DDM (p < 0.001; p < 0.001) particularly those with retinopathy (p < 0. 001; p < 0.001). Soluble E-Selectin levels were highest in the patient s with severe nonproliferative diabetic retinopathy (p < 0.001) and sV CAM-1 levels were highest in patients with proliferative diabetic reti nopathy (p < 0.01). In contrast soluble ICAM-1 levels were the same in patients and control subjects (p > 0.05). Soluble E-Selectin levels i n diabetic patients were correlated with the level of glycated haemogl obin (p < 0.05). Retinal endothelial cell migration-inducing (ECMI) ac tivity was increased in patients with IDDM (p < 0.01) in particular in those with retinopathy (p < 0.01). Furthermore, in vitro ECMI activit y could be blocked by antibodies to sVCAM-1 and sE-Selectin. These dat a point to a functional role for leucocyte adhesion in the microvascul opathy of diabetic retinopathy and may have implications for the induc tion of retinal angiogenesis.