May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Interleukin-10 Regulates Pathological Retinal Angiogenesis
Author Affiliations & Notes
  • D. S. Dace
    Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, Missouri
  • A. A. Khan
    Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, Missouri
  • R. S. Apte
    Ophthalmology and Visual Sciences, Washington University in St. Louis, St. Louis, Missouri
  • Footnotes
    Commercial Relationships  D.S. Dace, None; A.A. Khan, None; R.S. Apte, None.
  • Footnotes
    Support  NIH Grant 5 K08 EY016139-03 and a career development award from Research to Prevent Blindness
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2526. doi:https://doi.org/
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    • Get Citation

      D. S. Dace, A. A. Khan, R. S. Apte; Interleukin-10 Regulates Pathological Retinal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2526. doi: https://doi.org/.

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

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Abstract

Purpose: : Our laboratory has reported that interleukin-10 (IL-10) deficient mice demonstrate reduced choroidal neovascularization (CNV) compared to wild-type mice in a laser-injury model of CNV. This new study attempts to determine whether IL-10 deficiency influences retinal angiogenesis in a model of hypoxia-induced retinal neovascularization.

Methods: : P7 IL-10-/- and wild-type mice were exposed to 75% O2 for 5 days, followed by 5 days of normal O2 levels. Angiogenesis was evaluated using flat-mounts of fluorescein-perfused retinas and histology. Retinal inflammatory macrophages were characterized by fluorescent microscopy of perfused retinas. Gene expression of retinal macrophages was performed using quantitative real-time RT-PCR. Wild-type mice were treated with blocking antibodies to IL-10. The inhibition of vascular endothelial cell proliferation was assessed by treatment of wild-type and IL-10-/- macrophages with normoxic or hypoxic conditions.

Results: : Retinal neovascularization was decreased in IL-10-/- mice compared to wild-type control mice, as determined by fluorescent angiograms of retinal flatmounts and histology of whole globes. Ischemia resulted in a significant infiltrate of F4/80+ cells into the retina of both wild-type and IL-10-/- mice. Nitric oxide, a potential pro-angiogenic molecule in the retina, was highly upregulated in wild-type retinal macrophages but not in IL-10-/- retinal macrophages. Treatment of pups with blocking antibodies to IL-10 resulted in significantly less retinal angiogenesis compared to isotype control treated mice. IL-10-/- macrophages that were exposed to hypoxic conditions significantly inhibited the proliferation of vascular endothelial cells in vitro, whereas hypoxic wild-type macrophages did not.

Conclusions: : IL-10 regulates retinal neovascularization, and may be an attractive therapeutic target in order to suppress the development of blood vessels in response to retinopathy of prematurity (ROP) or diabetic retinopathy.

Keywords: retinal neovascularization • retinopathy of prematurity • hypoxia 
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