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K. Noda, S. Nakao, S. Zandi, Y. Mashima, A. Hafezi-Moghadam; Role of Vascular Adhesion Protein-1 on Leukocyte Transmigration in Diabetic Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):111.
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© ARVO (1962-2015); The Authors (2016-present)
Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule, mainly regulating the transmigration step of the leukocyte recruitment cascade. Leukocyte adhesion to retinal vessels is a predominant feature of experimental diabetic retinopathy (DR). In contrast to intercellular adhesion molecule (ICAM)-1, the role of VAP-1 in diabetic retina remains to be studied.
Long-Evans rats, weighing 200-250g, received either a single intraperitoneal (i.p.) injection of STZ (60mg/kg) in 0.05mM citrate buffer (pH4.5) or citrate buffer only after an overnight fast. Retinal expression level of VAP-1 was quantified by real time PCR. The specific VAP-1 inhibitor, U-V002, was administered by daily i.p. injections (0.3mg/kg). Leukocyte adhesion to retinal vessels was investigated in retinal flatmounts after staining with concanavalin-A. Leukocyte transmigration rate was investigated by in vivo acridine orange leukocyte staining (AOLS).
Leukocyte transmigration rate was significantly increased (39±9cells/0.5h; n=6) in the retina of diabetic rats, compared with that of normal controls (11±2cells/0.5h; n=6; P<0.05). VAP-1 inhibition significantly reduced leukocyte transmigration in diabetic animals (20±4cells/0.5h; n=5; P<0.05), compared with the vehicle-treated diabetic controls (34±4cells/0.5h; n=6). However, diabetic animals treated with the VAP-1 inhibitor did not show a significant difference in the number of firmly adhering leukocytes compared with the vehicle-treated diabetic animals (n=6 each; P=0.7).
The current data indicate the important role of VAP-1 for leukocyte transmigration, but not firm leukocyte adhesion, in diabetic retina. VAP-1 inhibition may be beneficial in the treatment and prevention of DR.
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