March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
Deficiency Of p105 ( NFB1) Increases Diabetes-induced Inflammation And Vascular Degeneration In The Retina
Author Affiliations & Notes
  • Alexander A. Veenstra
    Pharmacology, Case Western Reserve University, Cleveland, Ohio
  • Nader Sheibani
    Ophthalmology and Visual Sciences, Univ of Wisconsin-Madison, Madison, Wisconsin
  • Timothy S. Kern
    Department of Medicine, Case Western Reserve Univ, Cleveland, Ohio
  • Footnotes
    Commercial Relationships  Alexander A. Veenstra, None; Nader Sheibani, None; Timothy S. Kern, None
  • Footnotes
    Support  NIH Grant EY000300
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2433. doi:
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      Alexander A. Veenstra, Nader Sheibani, Timothy S. Kern; Deficiency Of p105 ( NFB1) Increases Diabetes-induced Inflammation And Vascular Degeneration In The Retina. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2433.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : Previous studies suggested that NFΚB (p50/p65) contributes to the retinal inflammation and capillary degeneration that are characteristic of early stages of diabetic retinopathy in mice. p50 and p105 (NFΚB1) (the precurser of p50) can form heterotetramers and homodimers (p50) that inhibit NFΚB-mediated transcription. We postulated that deletion of p105 would eliminate possible p50 (and p105) inhibition of NFΚB, and result in unrestrained inflammation and pathology in diabetes.

Methods: : Abnormalities characteristic of early stages of diabetic retinopathy were evaluated in mice lacking the precursor of p50,(p105).

Results: : Diabetes-induced increases in retinal capillary loss, superoxide generation and iNOS levels were significantly increased in mice lacking p105. Leukocyte superoxide generation was similarly increased. Murine retinal endothelial cells co-cultured with leukocytes from diabetic animals were killed in greater numbers when the leukocytes were isolated from diabetic animals lacking p105.

Conclusions: : p105/p50 negatively regulates diabetes-induced inflammation and vascular pathology of the retina, and its absence exacerbates diabetes-induced vascular disease, further demonstrating the role of NFΚB in development of diabetic retinopathy.

Keywords: diabetic retinopathy • inflammation • transcription 

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