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K. Noda, S. Nakao, S. Zandi, Y. Mashima, A. Hafezi-Moghadam; Vascular Adhesion Protein-1 Regulates Leukocyte Transmigration Rate in the Retina During Diabetes. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5895.
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© ARVO (1962-2015); The Authors (2016-present)
Vascular adhesion protein-1 (VAP-1), an endothelial adhesion molecule involved in leukocyte recruitment, also possesses semicarbazide-sensitive amine oxidase activity. Leukocyte adhesion to retinal vessels is a predominant feature of experimental diabetic retinopathy (DR). However, the role of VAP-1 in DR is unknown.
Diabetes was induced by i.p. injection of Streptozotocin in Long-Evans rats. The VAP-1 inhibitor, UV-002, was administered by daily i.p. injections (0.3mg/kg). Firm leukocyte adhesion was quantified in retinal flatmounts after staining with concanavalin-A. Leukocyte transmigration rate was quantified by in vivo acridine orange leukocyte staining (AOLS).
In diabetic rats, retinal leukocyte transmigration rate was significantly higher (39±9cells/0.5h; n=6), compared to normal controls (11±2cells/0.5h; n=6; P<0.05). With VAP-1 inhibition in diabetic animals, leukocyte transmigration rate was significantly reduced (20±4cells/0.5h; n=5; P<0.05), compared with the vehicle-treated diabetic controls (34±4cells/0.5h; n=6). However, firm adhesion of leukocytes in diabetic animals treated with the inhibitor did not differ significantly from vehicle-treated diabetic controls (n=6 each; P=0.7).
This work provides evidence for an important role of VAP-1 in the recruitment of leukocyte to the retina in experimental DR. Our results reveal the critical contribution of VAP-1 to leukocyte transmigration rate, with little impact on firm leukocyte adhesion in retinas of diabetic animals. VAP-1 inhibition might be beneficial in the treatment of DR.
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