July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
AIBP suppresses choroidal neovascularization (CNV) by enhancing cholesterol efflux
Author Affiliations & Notes
  • Yingbin Fu
    Ophthalmology, Baylor College of Medicine, Houston, Utah, United States
  • Mackenzie Parker
    Ophthalmology, Baylor College of Medicine, Houston, Utah, United States
  • Ling-Ping Zhu
    Cardiovascular Sciences, The Methodist Hospital Research Institute, Houston, Texas, United States
  • Qing Yan
    Cardiovascular Sciences, The Methodist Hospital Research Institute, Houston, Texas, United States
  • Nduka Enemchukwu
    Ophthalmology, Baylor College of Medicine, Houston, Utah, United States
  • Jun-dae Kim
    Cardiovascular Sciences, The Methodist Hospital Research Institute, Houston, Texas, United States
  • Longhou Fang
    Cardiovascular Sciences, The Methodist Hospital Research Institute, Houston, Texas, United States
  • Footnotes
    Commercial Relationships   Yingbin Fu, None; Mackenzie Parker, None; Ling-Ping Zhu, None; Qing Yan, None; Nduka Enemchukwu, None; Jun-dae Kim, None; Longhou Fang, None
  • Footnotes
    Support   2P30EY002520, Bright Focus Foundation Award in Macular Degeneration Research, The Sarah Campbell Blaffer Endowment in Ophthalmology (YF), unrestricted grants to the Department of Ophthalmology at Baylor College of Medicine from RPB.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3272. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Yingbin Fu, Mackenzie Parker, Ling-Ping Zhu, Qing Yan, Nduka Enemchukwu, Jun-dae Kim, Longhou Fang; AIBP suppresses choroidal neovascularization (CNV) by enhancing cholesterol efflux. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3272.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Dysregulated cholesterol homeostasis is implicated in the pathogenesis of age-related macular degeneration (AMD). However, the role of cholesterol removal in angiogenesis and the identity of its local regulators are poorly understood. We recently found that Apolipoprotein A-I binding protein (AIBP) accelerates cholesterol efflux from endothelial cells (ECs) to high-density lipoprotein (HDL), disrupts cholesterol-rich lipid rafts and inhibits VEGFR2 signaling. In addition, AIBP was shown to enhance cholesterol removal from macrophages and reduce inflammation. We hypothesize that AIBP can be an effective therapy for AMD by targeting VEGFR2 signaling in choroidal ECs and impaired cholesterol efflux in old macrophages. The objectives of this study are to determine the role of AIBP in physiological and pathological angiogenesis and to develop an AIBP-based therapy for AMD by enhancing cholesterol removal from ECs and macrophages.

Methods : We examined the effect of AIBP loss-of-function (Apoa1bp-/- or antibody neutralization) on physiological (choroid sprouting) and pathological angiogenesis (laser-induced CNV). We examined the efficacy of AIBP in inhibiting choroid angiogenesis in vitro (using choroidal EC line RF6A) and ex vivo (choroid sprouting assay). The effect of AIBP on the ability of macrophage in inhibiting EC proliferation was determined by EC and macrophage co-culture experiment. The effect of AIBP on laser-induced CNV was examined by intravitreal delivery of recombinant human AIBP and apoA-I.

Results : AIBP treatment significantly inhibits choroidal EC angiogenesis (50% reduction, p<0.001), and potently inhibits choroid sprouting (61% reduction, p= 0.035). Intravitreal delivery of AIBP and apoA-I robustly inhibits laser-induced CNV (50% reduction, p<0.001). AIBP deficiency markedly increases choroid sprouting (2.8 times, p = 0.043) and laser-induced CNV (2.1-fold, p<0.001) in Apoa1bp-/- mice compared with WT. AIBP neutralization caused a 1.9-fold (p<0.001) increase of the CNV area, suggesting that extracellular AIBP inhibits pathogenic angiogenesis. In addition, AIBP was markedly increased in CNV. EC and macrophage co-culture experiment are ongoing.

Conclusions : We have identified AIBP as a new regulator of cholesterol efflux, which regulates both physiological and pathological (e.g., CNV) angiogenesis. AIBP can be an effective therapy by enhancing cholesterol removal from ECs and macrophages.

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.

×