July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Elucidating the mechanism of endothelial caspase-9 after retinal vein occlusion.
Author Affiliations & Notes
  • Anna Michelle Potenski
    Pharmacology, Columbia University, New York, New York, United States
  • Maria Ivanna Avrutsky
    Pathology and Cell Biology, Columbia University, New York, New York, United States
  • Carol M Troy
    Pathology and Cell Biology, Columbia University, New York, New York, United States
    Neurology, Columbia University, New York, New York, United States
  • Footnotes
    Commercial Relationships   Anna Potenski, None; Maria Avrutsky, None; Carol Troy, Columbia University (P)
  • Footnotes
    Support  5T32EY013933-17
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4060. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Anna Michelle Potenski, Maria Ivanna Avrutsky, Carol M Troy; Elucidating the mechanism of endothelial caspase-9 after retinal vein occlusion.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4060.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : An induction of endothelial caspase-9 seen after retinal vein occlusion (RVO) sets off a signaling pathway causing edema, BRB breakdown, and eventual neuronal loss, however the downstream targets and exact mechanism of this pathway are still unknown. Using inducible endothelial cell caspase-9 knock out mice (C9 ECKO) and WT littermates, we will identify key factors that may be playing a role in this pathway and make the connection from endothelial cell insult to neuronal death.

Methods : 2-month-old C9 ECKO and WT littermate mice will undergo the RVO procedure previously described by Ebneter, et al. Using literature and database searches, we identified potential downstream targets of caspase-9 and are using this genetic model to test the hypothesis that they are involved in the pathway. Immunohistochemistry and western blotting will be used to determine the presence of these different substrates and to track the alteration in the amount of protein present between injured vs. non-injured mice as well as the C9ECKO vs. WT.

Results : This model has identified that caspase-7, a known downstream target of caspase-9, plays an essential role in the exacerbation of edema after injury. We see in the C9 ECKO mice that when there is no endothelial induction of caspase-9, there is also a loss of endothelial caspase-7. Since this is thought to be the first downstream effector of endothelial caspase-9, we looked into substrates for caspase-7 and found EMAP-II, an inflammatory cytokine that gets cleaved by caspase-7 into a mature form, recruiting monocytes and exacerbating the inflammatory and ischemic state of the tissue after injury. Using immunohistochemistry, we showed that EMAP-II is present in our model after injury.

Conclusions : Endothelial caspase-9 sets off a signaling cascade leading to neuronal death that starts with the activation of caspase-7. After caspase-7 gets activated, it cleaves EMAP-II which further increases the ischemic state after injury. Further substrates from caspase-9, caspase-7, and EMAP-II could be contributing to the breakdown of the BRB, increased edema, and eventual neuronal death. By eliminating the induction of endothelial caspase-9, we are able to prevent edema and BRB breakdown while preserving the neurons.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×