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.