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Alexander A. Veenstra, Ram Talahalli, Rose Gubitosi-Klug, Timothy S. Kern; Marrow-derived Cells Regulate The Development Of Diabetic Retinopathy In Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2577.
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We have previously reported that bone marrow-derived cells play a critical role in the development of diabetes-induced retinopathy. The present study investigates which subsets of white blood cells mediate this effect.
The contribution of leukocyte subtypes to diabetes induced capillary degeneration was evaluated using chimeric mice lacking G-CSFR (receptor for Granulocyte Colony Stimulating Factor) in marrow derived cells, and co-culture of retinal endothelial cells with peripheral blood leukocytes immunodepleted of different leukocyte subtypes. Leukocyte transmigration into the neural retina was evaluated using chimeric mice in which only the marrow derived cells expressed GFP
Neutrophils (and monocytes) play a major role in the retinopathy development, because diabetes induced degeneration of retinal capillaries was significantly inhibited in mice lacking G-CSFR in marrow-derived cells only. Immunodepletion of neutrophils or monocytes from purified leukocytes inhibited endothelial death otherwise observed when co-culturing leukocytes from diabetic animals with retinal endothelium. Leukostasis of both monocytes and neutrophils increased with diabetes in the retina, however, transmigration of these cells into the neural retina was not observed, suggesting leukocytes kill endothelial cells from within the vasculature. The addition of antioxidant (lipoic acid) or anti-FasL antibodies to the co-cultures reduced in vitro killing of endothelial death by leukocytes from diabetic animals.
We conclude that leukocytes, especially granulocytes, play a central role in the development of diabetic retinopathy by killing retinal capillary endothelial cells.
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