Neutrophils Are Associated With Capillary Closure in Spontaneously Diabetic Monkey Retinas

• Published in: Diabetes (New York, N.Y.) Vol. 54; no. 5; pp. 1534 - 1542
• Main Authors: KIM, Sahng Y, JOHNSON, Mary A, MCLEOD, D. Scott, ALEXANDER, Theresa, HANSEN, Barbara C, LUTTY, Gerard A
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.05.2005
• Subjects: Aneurysm - pathology; Animals; Biological and medical sciences; Capillaries - pathology; Capillaries - physiopathology; Diabetes; Diabetes Mellitus, Type 2 - pathology; Diabetes research; Diabetes. Impaired glucose tolerance; Diabetic retinopathy; Disease Models, Animal; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Evaluation; Eye and associated structures. Visual pathways and centers. Vision; Fundamental and applied biological sciences. Psychology; Genetic aspects; In Vitro Techniques; Macaca mulatta; Medical sciences; Neutrophils; Neutrophils - pathology; Neutrophils - physiology; Obesity - complications; Obesity - pathology; Vertebrates: nervous system and sense organs; United States; Endocrinopathy; Eye; Visual system; Vertebrata; Mammalia; Diabetes mellitus; Monkey; Primates; Retina; Neutrophil
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.54.5.1534

Neutrophils Are Associated With Capillary Closure in Spontaneously Diabetic Monkey Retinas Sahng Y. Kim 1 , Mary A. Johnson 2 , D. Scott McLeod 1 , Theresa Alexander 3 , Barbara C. Hansen 3 and Gerard A. Lutty 1 1 Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 2 Department of Ophthalmology, University of Maryland School of Medicine, Baltimore, Maryland 3 Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland Address correspondence and reprint requests to Gerard A. Lutty, PhD, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, 170 Woods Research Bldg., 600 North Wolfe St., Baltimore, MD 21287-9115. E-mail: galutty{at}jhmi.edu Abstract Type 2 diabetes develops spontaneously in obese aging rhesus monkeys ( Macaca mulatta ). This study investigates the association between polymorphonuclear leukocytes and development of retinopathy. Blood pressure and plasma glucose levels were determined in 15 diabetic and 6 nondiabetic monkeys. The plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were determined just before the start of the animal’s final decline and elective necropsy. Retinas were incubated for ADPase (labels viable retinal blood vessels) and nonspecific esterase (labels neutrophils) activities. Polymorphonuclear leukocytes were counted per millimeter squared of retina. After the retina was flat-embedded in glycol methacrylate, tissue sections were taken through areas of interest and observed microscopically. Elevated numbers of intravascular polymorphonuclear leukocytes were present adjacent to areas with retinal capillary nonperfusion. There were significantly more polymorphonuclear leukocytes per millimeter squared in diabetic retinas (6.91 ± 5.01) compared with normal retinas (1.45 ± 1.62, P = 0.018). Severity of hypertension in diabetes was also significantly associated with greater numbers of polymorphonuclear leukocytes ( P = 0.02). There was a significant positive exponential correlation between the number of polymorphonuclear leukocytes per millimeter squared and the level of total cholesterol ( R = 0.907), LDL cholesterol ( R = 0.875), the total cholesterol–to–HDL cholesterol ratio ( R = 0.86), and total triglycerides ( R = 0.888). This study demonstrates that severity of diabetes and the development of retinopathy are associated with increased numbers of polymorphonuclear leukocytes in the retina of diabetic monkeys. Hypertension, high plasma levels of LDL cholesterol and triglycerides, and low plasma levels of HDL cholesterol also are associated with increased polymorphonuclear leukocytes in retina. DD, disc diameter ICAM-1, intracellular adhesion molecule-1 ROS, reactive oxygen species Footnotes Accepted February 11, 2005. Received December 7, 2004. DIABETES