May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Vasoinhibins Prevent the Diabetic Retinopathy-Associated Vascular Leakage in vivo via Protein Phosphatase 2A-Dependent eNOS Inactivation
Author Affiliations & Notes
  • E. Arnold
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • J. Aranda
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • C. Garcia
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • S. Thebault
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • F. Lopez-Barrera
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • H. Quiroz-Mercado
    Asociacion para Evitar la Ceguera (APEC), Hospital Dr. Luis Sanchez Bulnes., Mexico D.F., Mexico
  • G. Martinez de la Escalera
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • C. Clapp
    Neurobiologia Celular y Molecular, Universidad Nacional Autonoma de Mexico, Queretaro, Mexico
  • Footnotes
    Commercial Relationships  E. Arnold, None; J. Aranda, None; C. Garcia, None; S. Thebault, None; F. Lopez-Barrera, None; H. Quiroz-Mercado, None; G. Martinez de la Escalera, None; C. Clapp, None.
  • Footnotes
    Support  CONACYT (grants Salud 2-2004-CO2-16 and 49292)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1347. doi:https://doi.org/
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      E. Arnold, J. Aranda, C. Garcia, S. Thebault, F. Lopez-Barrera, H. Quiroz-Mercado, G. Martinez de la Escalera, C. Clapp; Vasoinhibins Prevent the Diabetic Retinopathy-Associated Vascular Leakage in vivo via Protein Phosphatase 2A-Dependent eNOS Inactivation. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1347. doi: https://doi.org/.

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

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Abstract

Purpose: : Vasoinhibins are a family of peptides derived from prolactin that inhibit angiogenesis and vasodilation in the retina. Here, we evaluated whether vasoinhibins prevent increased retinal vascular permeability (RVP) in response to intravitreous injection of VEGF or of vitreous from patients with diabetic retinopathy (DR). We further analyzed whether this effect occurs via protein phosphatase 2A (PP2A)-dependent dephosphorylation/inactivation of endothelial nitric oxide synthase (eNOS).

Methods: : Wistar rats were injected intravitreally with VEGF (300 ng), or with 2 µl of human vitreous from patients with DR or non-diabetic corpse donors, with or without vasoinhibins (1µg). RVP was investigated by the Evans blue method. Retinal NOS activity and eNOS phosphorylation were measured by the [3H]L-citrulline assay and Western blots, respectively.

Results: : Vasoinhibins blocked RVP elevated in response to intravitreous injection of VEGF or of vitreous from patients with DR. The extent of inhibition by vasoinhibins was similar to that following immunodepletion of VEGF from DR vitreous or blockage of NO synthesis with L-NAME. Vasoinhibins prevented VEGF-induced eNOS phosphorylation at Ser1179, and NOS activation in the retina. PP2A leads to eNOS dephosphorylation at Ser1179 and the PP2A inhibitor okadaic acid blocked the effect of vasoinhibins on RVP.

Conclusions: : The present study shows that vasoinhibins prevent the DR-associated increase of RVP. The effect involves the inhibition of VEGF-induced eNOS activation due to dephosphorylation of eNOS by PP2A. Our findings suggest that vasoinhibins may be developed as protective agents against diabetic macular edema.

Keywords: diabetic retinopathy • nitric oxide • vascular endothelial growth factor 
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