TY - JOUR
T1 - Vascular adhesion protein-1 regulates leukocyte transmigration rate in the retina during diabetes
AU - Noda, Kousuke
AU - Nakao, Shintaro
AU - Zandi, Souska
AU - Engelstädter, Verena
AU - Mashima, Yukihiko
AU - Hafezi-Moghadam, Ali
N1 - Funding Information:
We thank Alexander Schering for compiling the 3D confocal images. This work was supported by NIH grants AI050775 (AHM) and HL086933 (Alan Cross, University of Maryland), research funds from R-TECH-UENO, Bausch & Lomb Fellowships (K.N. and S.N.), a Fellowship Award from the Japan Eye Bank Association (K.N. and S.N.), and NEI core grant EY14104. We are indebted to the Massachusetts Lions Eye Research Fund Inc. for generous funds provided for laboratory equipment used in this project. We would like to thank Marion W. and Edward F. Knight AMD Fund, Research to Prevent Blindness, and American Health Assistance Foundation for their support.
PY - 2009/11
Y1 - 2009/11
N2 - Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule that possesses semicarbazide-sensitive amine oxidase (SSAO) activity and is involved in leukocyte recruitment. Leukocyte adhesion to retinal vessels is a predominant feature of experimentally induced diabetic retinopathy (DR). However, the role of VAP-1 in this process is unknown. Diabetes was induced by i.p. injection of Streptozotocin in Long-Evans rats. The specific inhibitor of VAP-1, UV-002, was administered by daily i.p. injections. The expression of VAP-1 mRNA in the retinal extracts of normal and diabetic animals was measured by real-time quantitative polymerase chain reaction (PCR). Firm leukocyte adhesion was quantified in retinal flatmounts after intravascular staining with concanavalin A (ConA). Leukocyte transmigration rate was quantified by in vivo acridine orange leukocyte staining (AOLS). In diabetic rats, the rate of leukocyte transmigration into the retinal tissues of live animals was significantly increased, as determined by AOLS. When diabetic animals were treated with daily injections of the VAP-1 inhibitor (0.3 mg/kg), leukocyte transmigration rate was significantly reduced (P < 0.05). However, firm adhesion of leukocytes in diabetic animals treated with the inhibitor did not differ significantly from vehicle-treated diabetic controls. 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, with little impact on firm leukocyte adhesion in the retinas of diabetic animals. VAP-1 inhibition might be beneficial in the treatment of DR.
AB - Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule that possesses semicarbazide-sensitive amine oxidase (SSAO) activity and is involved in leukocyte recruitment. Leukocyte adhesion to retinal vessels is a predominant feature of experimentally induced diabetic retinopathy (DR). However, the role of VAP-1 in this process is unknown. Diabetes was induced by i.p. injection of Streptozotocin in Long-Evans rats. The specific inhibitor of VAP-1, UV-002, was administered by daily i.p. injections. The expression of VAP-1 mRNA in the retinal extracts of normal and diabetic animals was measured by real-time quantitative polymerase chain reaction (PCR). Firm leukocyte adhesion was quantified in retinal flatmounts after intravascular staining with concanavalin A (ConA). Leukocyte transmigration rate was quantified by in vivo acridine orange leukocyte staining (AOLS). In diabetic rats, the rate of leukocyte transmigration into the retinal tissues of live animals was significantly increased, as determined by AOLS. When diabetic animals were treated with daily injections of the VAP-1 inhibitor (0.3 mg/kg), leukocyte transmigration rate was significantly reduced (P < 0.05). However, firm adhesion of leukocytes in diabetic animals treated with the inhibitor did not differ significantly from vehicle-treated diabetic controls. 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, with little impact on firm leukocyte adhesion in the retinas of diabetic animals. VAP-1 inhibition might be beneficial in the treatment of DR.
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U2 - 10.1016/j.exer.2009.07.010
DO - 10.1016/j.exer.2009.07.010
M3 - Article
C2 - 19635478
AN - SCOPUS:70349456530
SN - 0014-4835
VL - 89
SP - 774
EP - 781
JO - Experimental Eye Research
JF - Experimental Eye Research
IS - 5
ER -
