April 2010
Volume 51, Issue 13
ARVO Annual Meeting Abstract  |   April 2010
Leukocytes Regulate Retinal Capillary Degeneration in Diabetes Via Generation of Leukotrienes
Author Affiliations & Notes
  • R. A. Gubitosi-Klug
    Pediatrics, Rainbow Babies &Childs Hosp/CWRU, Cleveland, Ohio
  • R. Talahalli
    Pediatrics, Rainbow Babies &Childs Hosp/CWRU, Cleveland, Ohio
  • Footnotes
    Commercial Relationships  R.A. Gubitosi-Klug, None; R. Talahalli, None.
  • Footnotes
    Support  NEI KO8EY016833
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3825. doi:
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      R. A. Gubitosi-Klug, R. Talahalli; Leukocytes Regulate Retinal Capillary Degeneration in Diabetes Via Generation of Leukotrienes. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3825.

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

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Purpose: : Degeneration of retinal capillaries in diabetes may result from a chronic inflammatory process that damages the endothelium. Leukocytes participate in inflammatory responses through the generation of potent pro-inflammatory mediators such as the leukotrienes. We investigated the role of the leukocyte and leukotriene generation in inducing retinal inflammation and retinal capillary degeneration in the diabetic mouse.

Methods: : We generated chimeric mice which lacked the ability to generate leukotrienes by transplanting 5-lipoxygenase deficient (5LO-/-) bone marrow cells into non-diabetic, wild-type (WT) mice{5LO-/- → ND.WT} and into streptozotocin-induced diabetic, wild-type mice {5LO-/- → SD.WT}. Comparisons were made to 1) chimeric mice using the reverse strategy of transplanting WT bone marrow cells into 5-lipoxygenase deficient mice{WT→ND.5LO -/- and WT →SD.5LO-/-} and to 2) non-chimeric, standard non-diabetic and diabetic WT mice. In vitro experiments were carried out with mouse leukocytes from diabetic and non-diabetic WT and 5LO-/- mice co-cultured with mouse retinal microvascular endothelial cells.

Results: : Diabetes-induced leukocyte adherence and retinal superoxide generation were significantly reduced in retinas from the leukotriene deficient mice {5LO-/- → SD.WT}, compared to both{WT →SD.5LO-/-} and non-chimeric, diabetic WT mice. (p<0.05) These findings correlated with retinal histology where a significant decrease in the capillary degeneration and pericyte loss was seen in {5LO-/- → SD.WT}compared to both{WT →SD.5LO-/-} and diabetic WT mice. (p<0.05) Immunostaining of paraffin sections of retinas from chimeras indicated a significant decrease in the diabetes-induced increase in expression of NF-kB p65, ICAM-1, MCP-1 and TNF-α in retinas from chimeras containing 5LO-/- deficient bone marrow cells. Co-cultures of peripheral blood leukocytes from diabetic WT mice with retinal microvascular endothelial cells resulted in increased endothelial cell death compared to endothelial cells co-cultured with non-diabetic WT leukocytes. In contrast, retinal microvascular endothelial cell death was not increased when cells were cultured with diabetic 5LO-/- leukocytes. Under co-culture conditions, diabetic WT leukocytes induced a translocation of NF-kB p65 to the nucleus of mouse retinal microvascular endothelial cells, which was not detected in co-cultures with diabetic 5LO-/- leukocytes.

Conclusions: : In vivo and in vitro data suggest the involvement of leukocytes and leukotrienes in the regulation of inflammation and capillary degeneration in diabetic retinopathy.

Keywords: diabetic retinopathy • eicosanoids 

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