June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Adult Notch3 Deficient Mice Exhibit Extensive Mural Cell Loss in the Retinal Vasculature
Author Affiliations & Notes
  • Alex A. Bigger-Allen
    ophthalmology, Schepens Eye Research Institute/Mass Eye and Ear, Boston, MA
  • mark Graham
    ophthalmology, Schepens Eye Research Institute/Mass Eye and Ear, Boston, MA
  • Joseph F Arboleda-Velasquez
    ophthalmology, Schepens Eye Research Institute/Mass Eye and Ear, Boston, MA
  • Vincent Primo
    ophthalmology, Schepens Eye Research Institute/Mass Eye and Ear, Boston, MA
  • Patricia A D'Amore
    ophthalmology, Schepens Eye Research Institute/Mass Eye and Ear, Boston, MA
  • Footnotes
    Commercial Relationships Alex Bigger-Allen, None; mark Graham, None; Joseph Arboleda-Velasquez, None; Vincent Primo, None; Patricia D'Amore, AGTC (C), Eleven Biotheroputics (C)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3384. doi:
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      Alex A. Bigger-Allen, mark Graham, Joseph F Arboleda-Velasquez, Vincent Primo, Patricia A D'Amore; Adult Notch3 Deficient Mice Exhibit Extensive Mural Cell Loss in the Retinal Vasculature. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3384.

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

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Abstract
 
Purpose
 

Vascular development is mediated in part by interactions between endothelial cells (ECS) and mural cells. This heterotypic signaling plays a critical role in the formation, maturation and stability of the blood vessels. Prior work using cell culture and animal models has implicated the Notch signaling pathway in vascular development and stability. We have previously demonstrated a critical role for Notch signaling in mural cell survival in vitro. In the present work, we examined the role of Notch signaling in the adult microvasculature in vivo.

 
Methods
 

Retinas were dissected from 200-day-old mice including wild type (WT), n = 4 and from Notch 3 knockout mice (Notch 3 -/-), n = 4. Flat mounts were stained by immunofluorescence using antisera against a-smooth muscle actin (αSMA) conjugated to Cy3 fluorophore as well as lectin conjugated to Alexa 488 fluorophore. Mural cell coverage was quantified using Image J by dividing the total mural cell area by the total vascularized area.

 
Results
 

The retinal vasculature of adult Notch 3 knockout mice had 48% ± 14.22, p < 0.001 less aSMA positive area compared to the C57BL/6J control. Arterial vessels from the base of the optic nerve to as far as secondary and tertiary branches of the arteries exhibited significant lengths devoid of smooth muscle cells investment (Fig 1). Areas of vessels that were lacking smooth muscle cells displayed vessel dilation, which is reminiscent of the microaneurysms that characterize background diabetic retinopathy.

 
Conclusions
 

The absence of mural cells in 6- month-old retinal vessels of Notch 3 knockout mice suggests that Notch signaling is necessary for the stability and/or survival of mural cells in the adult. Further, these data support the hypothesis that the loss of mural cells contributes to the retinal degeneration observed in diabetic retinopathy.  

 
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