Muller Cells Upregulate Angiopoietin-like 4 To Promote Vascular Permeability in Ischemic Retinal Disease

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Unmet Need
In proliferative diabetic retinopathy (PDR), the most vision-threatening consequence of diabetic eye disease, is retinal ischemia leading to increased expression of angiogenic factors that promote neovascularization. Although therapies targeting the potent angiogenic mediator vascular endothelial growth factor (VEGF) have been remarkably successful for the treatment of diabetic macular edema, this approach has not proven sufficient to prevent the development of retinal neovascularization, implicating additional angiogenic factor(s) in PDR pathogenesis.
Technology Overview
Johns Hopkins researchers have identified a novel therapeutic target, angiopoietin-like 4 (ANGPTL4), for the treatment of ocular neovascular disease and which may have broad implications for the treatment of other diseases dependent on pathologic angiogenesis. Using gene expression analysis, a novel cytokine, ANGPTL4, which is upregulated by hypoxia inducible factor-1(HIF-1) in hypoxic Müller cells (in vitro) and in the ischemic inner retina (in vivo). ANGPTL4 is critical and sufficient for the promotion of vessel permeability and angiogenesis. Data suggest that targeting both ANGPTL4 and VEGF may be necessary for effective treatment or prevention of diabetic eye disease.
Stage of Development
In vitro and in vivo data are available.
Babapoor-Farrokhran S. et al. PNAS June 9, 2015. 112 (23) E3030-E3039
Xin X et al. PNAS September 3, 2013. 110 (36) E3425-E3434
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Sonriza Ford
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