September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Investigation of VEGF165 induced retinal vascular inflammation in vitro
Author Affiliations & Notes
  • Ashley Mackey
    Ophthalmology, Schepens Eye Research Institute/Mass Eye and Ear, Boston, Massachusetts, United States
  • Yin Shan Eric Ng
    Ophthalmology, Schepens Eye Research Institute/Mass Eye and Ear, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Ashley Mackey, None; Yin Shan Eric Ng, None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 3199. doi:
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      Ashley Mackey, Yin Shan Eric Ng; Investigation of VEGF165 induced retinal vascular inflammation in vitro. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3199.

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

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Abstract

Purpose : Vascular inflammation or leukostasis has been implicated in the pathogenesis of many different eye conditions such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and retinopathy of prematurity (ROP), but how exactly inflammation is regulated still remains largely unknown. VEGF165 has been correlated with increased leukostasis during different stages of AMD and DR. Preliminary data suggest that intravitreally injected murine VEGF164 potentially induced leukostasis whereas VEGF120 isoform did not. The goal of this study was to determine the inflammation potential of VEGF165 in vitro and identify the mechanisms by which VEGF165 induces inflammation.

Methods : To determine the pro-inflammatory response of VEGF165 and VEGF120 in vitro, cultured human retinal endothelial cells (HREC) were treated with equimolar amounts of VEGF (119 pM) and qPCR analysis was used to assess the changes in pro-inflammatory genes expression. To elucidate the mechanism by which VEGF165 induced an inflammatory response, we inhibited different branches of the VEGFR2 signaling pathway (MAPK, PI3K and P38) using specific small molecule inhibitors and analyzed their effects on VEGF165-mediated pro-inflammatory response by qPCR and western blotting analyses.

Results : In comparison to HREC cells treated with VEGF120, VEGF165 treatment increased mRNA levels of VCAM-1, E-selectin (ES) and Tissue Factor (TF). Inhibition of P38 MAPK prevented this increase in mRNA levels of TF, VCAM1 and ES, while inhibition of PI3K signaling suppressed the increase in mRNA levels of VCAM1 and ES. Inhibition of MAPK signaling did not suppress the VEGF165 induced upregulation of TF, VCAM1 or ES.

Conclusions : These studies demonstrate that treatment with VEGF165 can induce and promote an inflammatory response by retinal endothelial cells when compared to VEGF120. Both PI3K and P38 MAPK activity could potentially play a role in inducing inflammation.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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