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G. Li, X. WANG, R. Talahalli, R. A. Gubitosi-Klug, T. S. KERN; Bone Marrow-derived Cells Play a Critical Role in the Development of Early Stages of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):23. doi: https://doi.org/.
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Whole body inhibition (or deletion) of PARP-1 or iNOS significantly inhibit degeneration of retinal capillaries in diabetes. Which cell types are responsible for this effect is not known. We present data demonstrating that cells derived from bone marrow play a critical role in the vascular degeneration and dysfunction of diabetic retinopathy.
Chimeric mice which lacked either iNOS or PARP-1 only in their marrow-derived cells (iNOS-/-→WT or PARP-/- →WT) or vice versa (lacked iNOS (WT→ iNOS-/-) or PARP-1 (WT→ PARP-/-)from all cells except marrow-derived cells) were generated by us. Control animals had bone marrow from wild type animals injected into wild type animals (WT→WT). At 10 weeks of diabetes, proinflammatory cytokines in the retina were assessed using the real-time PCR, and accumulation of albumin in the retina (a possible marker of vascular permeability) was investigated by immunohistological techniques. At 30 weeks of diabetes, the degeneration of retina capillaries was quantitated using the trypsin digest method.
Diabetic (WT→WT) controls developed the expected increase in proinflammatory cytokines and accumulation of albumin in neuronal retina at 10 weeks of diabetes, and degeneration of retinal capillaries at 30 weeks of diabetes. In contrast, all of these defects were inhibited in diabetic chimeras lacking either iNOS or PARP-1from bone marrow cells. Reverse chimeras lacking iNOS or PARP-1 from all cells except bone marrow cells still developed these lesions.
We conclude that inflammatory processes within white blood cells or other marrow-derived cells play a central role in the development of early stages of diabetic retinopathy, and that inflammatory processes in marrow-derived cells offer a new therapeutic target to inhibit the development of diabetic complications.
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