June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Modulation of P75NTR protects against ischemic retinopathy: Possible contribution of TrkA receptor
Author Affiliations & Notes
  • Sally L Elshaer
    Clinical and Administrative Pharmacy, University of Georgia, Augusta, GA
    Charlie Norwood VA Medical Center,, Augusta, GA
  • Azza B El-Remessy
    Clinical and Administrative Pharmacy, University of Georgia, Augusta, GA
    Charlie Norwood VA Medical Center,, Augusta, GA
  • William Hill
    Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA
  • Footnotes
    Commercial Relationships Sally Elshaer, None; Azza El-Remessy, None; William Hill, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4276. doi:
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    • Get Citation

      Sally L Elshaer, Azza B El-Remessy, William Hill; Modulation of P75NTR protects against ischemic retinopathy: Possible contribution of TrkA receptor. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4276.

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

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Abstract

Purpose: We have previously shown that, inhibition of the neurotrophin death receptor; p75NTR enhanced angiogenic response in retinal endothelial cells (EC). Genetic deletion of p75NTR accelerated reparative angiogenesis and prevented pathological neovascularization in oxygen-induced retinopathy model. The aim of this study is to investigate the possible underlying mechanisms of the protective effects of modulating p75NTR in restoring angiogenesis in ischemic retina.

Methods: Number of tip-cells was compared between WT and p75KO at postnatal day 5. WT and p75KO mice were subjected to oxygen-induced retinopathy or ischemia reperfusion models. Homing of MSCs to ischemic retina vasculature was evaluated. Retinal EC or murine mesenchymal stem cells (MSCs) were treated with p75NTR inhibitor and the angiogenic response was detected.

Results: Deletion of p75NTR enhanced physiological angiogenesis as indicated by significantly higher number of tip cells in p75KO mice pups compared to their WT littermates. MSCs showed better homing to ischemic retinal vasculature in p75KO mice compared to WT. Deletion of p75NTR restored NGF level, induced activation of TrkA, ERK1,2 and Akt in ischemic retinas. In-vitro, inhibiting p75NTR induced TrkA, ERK1,2 and Akt in EC cultures.

Conclusions: Our results showed that deletion of p75NTR protects against ischemia in retina by mechanisms involving both restored NGF/TrkA angiogenic signal and enhanced homing of MSCs to support growing vasculature. Thus, inhibition of p75NTR can provide potential therapeutic targets for ischemic retinopathy.

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