Purchase this article with an account.
S. Miyahara, K. Noda, T. Nakazawa, T. Hisatomi, J.W. Miller, E. Gragoudas, A. Hafezi–Moghadam; VLA–4 Blockade Attenuates Leukocyte Accumulation in the Retinal Vessels of Streptozotocin–Induced Diabetic Rats . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1736.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Leukocytes play a crucial role in the pathogenesis of diabetic retinopathy. A variety of adhesion molecules contribute to the recruitment of leukocytes to the diabetic endothelium. However, the role of Very Late Antigen 4 (VLA–4) and its endothelial ligand, Vascular Cell Adhesion Molecule–1 (VCAM–1), in this process is not well understood. Therefore, we investigated the effect of VLA–4 blockade on leukocyte accumulation in the retinas of diabetic animals in vivo.
Diabetes was induced in Long–Evans rats by intraperitoneal injection of streptozotocin (60 mg/kg). Anti rat VLA–4 monoclonal antibody (1mg/day) or an isotype–matched control IgG was injected intraperitoneally for 2 weeks after diabetes induction. Leukostasis in the retinal microcirculation was quantified by Acridine Orange Fluorography (AOF).
We found on average 13.0 ± 2.4 leukocytes per retina in the group of non–diabetic animals, 41.2 ± 0.7 in the retina of diabetic animals treated with the control antibody, and 15.7 ± 1.4 in the retina of diabetic animals treated with the neutralizing anti–VLA–4 antibody. In comparison, treatment with the anti–VLA–4 neutralizing antibody significantly suppressed the number of leukocytes accumulated in the retinal vessels of diabetic animals by 61.9% (P < 0.0001).
These data suggest an important role for the interaction of VLA–4 with endothelial VCAM–1 in retinal leukocyte accumulation during diabetes. VLA–4 blockade may offer a new approach for prevention and treatment of diabetic retinopathy, by diminishing inflammatory leukocyte recruitment.
This PDF is available to Subscribers Only