Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition.
Diabetic retinopathy is a leading cause of adult vision loss and blindness. Much of the retinal damage that characterizes the disease results from 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.
Miyamoto
K
K
Laboratory for Surgical Research, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Khosrof
S
S
Bursell
S E
SE
Rohan
R
R
Murata
T
T
Clermont
A C
AC
Aiello
L P
LP
Ogura
Y
Y
Adamis
A P
AP
D000165:Acridine Orange / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D005451:Fluorescein Angiography; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D018921:Leukostasis / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D020318:Rats, Long-Evans; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1; D000165:Acridine Orange