Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition

被引:648
作者
Miyamoto, K
Khosrof, S
Bursell, SE
Rohan, R
Murata, T
Clermont, AC
Aiello, LP
Ogura, Y
Adamis, AP [1 ]
机构
[1] Harvard Univ, Childrens Hosp, Sch Med, Surg Res Lab,Joslin Diabet Ctr, Boston, MA 02115 USA
[2] Harvard Univ, Childrens Hosp, Sch Med, Dept Ophthalmol,Joslin Diabet Ctr, Boston, MA 02115 USA
[3] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA
[4] Nagoya City Univ, Sch Med, Dept Ophthalmol, Nagoya, Aichi 467, Japan
关键词
D O I
10.1073/pnas.96.19.10836
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Diabetic retinopathy is a leading cause of adult vision loss and blindness, Much of the retinal damage that characterizes the disease results horn retinal vascular leakage and nonperfusion, This study shows that diabetic retinal vascular leakage and nonperfusion are temporally and spatially associated with retinal leukocyte stasis (leukostasis) in the rat model of streptozotocin-induced diabetes. Retinal leukostasis increases within days of developing diabetes and correlates with the increased expression of retinal intercellular adhesion molecule-1 (ICAM-1), ICAM-1 blockade with a mAb prevents diabetic retinal leukostasis and vascular leakage by 48.5% and 85.6%, respectively. These data identify the causal role of leukocytes in the pathogenesis of diabetic retinopathy and establish the potential utility of ICAM-1 inhibition as a therapeutic strategy for the prevention of diabetic retinopathy.
引用
收藏
页码:10836 / 10841
页数:6
相关论文
共 21 条
[1]   Spontaneous regression of neovascularization at the disk and elsewhere in diabetic retinopathy [J].
Bandello, F ;
Gass, JDM ;
Lattanzio, R ;
Brancato, R .
AMERICAN JOURNAL OF OPHTHALMOLOGY, 1996, 122 (04) :494-501
[2]   Loss of the tight junction proteins occludin and zonula occludens-1 from cerebral vascular endothelium during neutrophil-induced blood-brain barrier breakdown in vivo [J].
Bolton, SJ ;
Anthony, DC ;
Perry, VH .
NEUROSCIENCE, 1998, 86 (04) :1245-1257
[3]   Polymorphonuclear leukocyte adhesion triggers the disorganization of endothelial cell-to-cell adherens junctions [J].
DelMaschio, A ;
Zanetti, A ;
Corada, M ;
Rival, Y ;
Ruco, L ;
Lampugnani, MG ;
Dejana, E .
JOURNAL OF CELL BIOLOGY, 1996, 135 (02) :497-510
[4]  
KAWASAKI K, 1993, J IMMUNOL, V150, P1074
[5]   ANTIBODY TO INTERCELLULAR-ADHESION MOLECULE-1 PROTECTS THE KIDNEY AGAINST ISCHEMIC-INJURY [J].
KELLY, KJ ;
WILLIAMS, WW ;
COLVIN, RB ;
BONVENTRE, JV .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (02) :812-816
[6]   MOLECULAR DETERMINANTS OF REPERFUSION-INDUCED LEUKOCYTE ADHESION AND VASCULAR PROTEIN LEAKAGE [J].
KUROSE, I ;
ANDERSON, DC ;
MIYASAKA, M ;
TAMATANI, T ;
PAULSON, JC ;
TODD, RF ;
RUSCHE, JR ;
GRANGER, DN .
CIRCULATION RESEARCH, 1994, 74 (02) :336-343
[7]  
LUSCINSKAS FW, 1991, J IMMUNOL, V146, P1617
[8]  
Lutty GA, 1997, AM J PATHOL, V151, P707
[9]  
MCLEOD DS, 1995, AM J PATHOL, V147, P642
[10]  
Miyamoto K, 1996, INVEST OPHTH VIS SCI, V37, P2708