April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Bone Marrow-derived Cells Play a Critical Role in the Development of Early Stages of Diabetic Retinopathy
Author Affiliations & Notes
  • G. Li
    Medicine,
    Case Western Reserve University, Cleveland, Ohio
  • X. WANG
    GENETICS,
    Case Western Reserve University, Cleveland, Ohio
  • R. Talahalli
    Department of Pediatrics and Center for Diabetes Research, Case Medical Center, Cleveland, Ohio
  • R. A. Gubitosi-Klug
    Department of Pediatrics and Center for Diabetes Research, Case Medical Center, Cleveland, Ohio
  • T. S. KERN
    Medicine,
    Case Western Reserve University, Cleveland, Ohio
    Veterans Administration Medical Center Research Service 151, Cleveland, Ohio
  • Footnotes
    Commercial Relationships  G. Li, None; X. Wang, None; R. Talahalli, None; R.A. Gubitosi-Klug, None; T.S. Kern, None.
  • Footnotes
    Support  NIH (R01EY00300) and the Medical Research Service of the Department of Veteran Affairs
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 23. doi:https://doi.org/
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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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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: diabetic retinopathy 
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