April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Angiopoietin-like 4 is a Potent Angiogenic Factor in Patients with Proliferative Diabetic Retinopathy
Author Affiliations & Notes
  • Kathleen Josephine Jee
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Savalan Babapoor
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Junaid Hassan
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Yassine Daoud
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Sharon D Solomon
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Gregg L Semenza
    Departments of Pediatrics, Medicine, Oncology, and Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD
  • Silvia Montaner
    Department of Oncology and Diagnostic Sciences, University of Maryland Greenebaum Cancer Center, Baltimore, MD
  • Akrit Sodhi
    Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD
  • Footnotes
    Commercial Relationships Kathleen Jee, None; Savalan Babapoor, None; Junaid Hassan, None; Yassine Daoud, None; Sharon Solomon, None; Gregg Semenza, None; Silvia Montaner, None; Akrit Sodhi, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5820. doi:
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      Kathleen Josephine Jee, Savalan Babapoor, Junaid Hassan, Yassine Daoud, Sharon D Solomon, Gregg L Semenza, Silvia Montaner, Akrit Sodhi; Angiopoietin-like 4 is a Potent Angiogenic Factor in Patients with Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5820.

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

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Abstract

Purpose: Proliferative diabetic retinopathy (PDR) is an ischemic retinopathy characterized by retinal neovascularization (NV). In a recent multicenter randomized controlled clinical trial, monthly injection with a monoclonal antibody directed against the potent angiogenic cytokine, vascular endothelial growth factor (VEGF), resulted in a 2/3 reduction - or delay - in the progression to PDR compared to control (sham) treated patients. Although encouraging, this suggests that other factor(s) may drive the development of NV in approximately 1/3 of these patients. Several cytokines have been suggested to promote retinal NV in ischemic retinal disease. We have recently identified angiopoietin-like 4 (ANGPTL4) as a potent angiogenic factor upregulated in animal models of ischemic retinal disease. Here we examine the levels of ANGPTL4 in the aqueous fluid (AF) of patients with diabetic retinopathy.

Methods: The AF from non-diabetic control (n=60) and diabetic (n=42) patients was collected from consenting patients undergoing cataract or vitrectomy surgery. Levels of VEGF and ANGPTL4 were assessed using an enzyme-linked immunosorbent assay (ELISA). Angiogenic activity was evaluated using an in vitro tubule formation assay.

Results: ELISA analysis of the AF from diabetic patients revealed 38.5% of PDR patients had VEGF levels below the average level detected in control patients. Surprisingly, 100% of AF from low-VEGF PDR patients remained angiogenic (p<0.001). Using in vitro and in vivo approaches, we identified ANGPTL4 as a potent angiogenic cytokine with increased expression in ischemic retinopathies. Levels of ANGPTL4 were increased by 6.7-fold in PDR compared to control patients (p<0.001). Use of an ANGPTL4 blocking antibody inhibited the angiogenic potential of AF of PDR patients with low-VEGF/high-ANGPTL4 levels.

Conclusions: Collectively, our results suggest that inhibition of ANGPTL4 may be an effective approach for the treatment of PDR.

Keywords: 499 diabetic retinopathy • 700 retinal neovascularization • 572 ischemia  
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