Marrow-Derived Cells Regulate the Development of Early Diabetic Retinopathy and Tactile Allodynia in Mice

• Published in: Diabetes (New York, N.Y.) Vol. 61; no. 12; pp. 3294 - 3303
• Main Authors: GUANGYUAN LI, VEENSTRA, Alexander A, TALAHALLI, Ramaprasad R, XIAOQI WANG, GUBITOSI-KLUG, Rose A, SHEIBANI, Nader, KERN, Timothy S
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.12.2012
• Subjects: Animals; Biological and medical sciences; Blood; Bone marrow; Bone marrow cells; Bone Marrow Cells - metabolism; Complications; Development and progression; Diabetes; Diabetes. Impaired glucose tolerance; Diabetic retinopathy; Diabetic Retinopathy - metabolism; Diabetic Retinopathy - pathology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Genetic aspects; Granulocytes; Hyperalgesia - metabolism; Hyperalgesia - pathology; Inflammation; Leukocytes; Medical sciences; Mice; Neutrophils; Neutrophils - metabolism; Nitric oxide; Nitric Oxide Synthase Type II - metabolism; Ophthalmology; Pain; Physiological aspects; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - metabolism; Proteins; Retina; Retina - metabolism; Retina - pathology; Retinopathies; Risk factors; Superoxides - metabolism; United States; Endocrinopathy; Allodynia; Eye disease; Vertebrata; Mammalia; Retinopathy; Mouse; Animal; Diabetes mellitus; Rodentia; Development
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db11-1249

The hypothesis that marrow-derived cells, and specifically proinflammatory proteins in those cells, play a critical role in the development of diabetes-induced retinopathy and tactile allodynia was investigated. Abnormalities characteristic of the early stages of retinopathy and allodynia were measured in chimeric mice lacking inducible nitric oxide synthase (iNOS) or poly(ADP-ribosyl) polymerase (PARP1) in only their marrow-derived cells. Diabetes-induced capillary degeneration, proinflammatory changes, and superoxide production in the retina and allodynia were inhibited in diabetic animals in which iNOS or PARP1 was deleted from bone marrow cells only. Of the various marrow cells, neutrophils (and monocytes) play a major role in retinopathy development, because retinal capillary degeneration likewise was significantly inhibited in diabetic mice lacking the receptor for granulocyte colony-stimulating factor in their marrow-derived cells. Immunodepletion of neutrophils or monocytes inhibited the endothelial death otherwise observed when coculturing leukocytes from wild-type diabetic animals with retinal endothelium. iNOS and PARP1 are known to play a role in inflammatory processes, and we conclude that proinflammatory processes within marrow-derived cells play a central role in the development of diabetes complications in the retina and nerve.