ECE2014 Poster Presentations Diabetes complications (59 abstracts)
Vasoinhibins are natural inhibitors of angiogenesis in the vitreous and are impaired in patients with diabetic retinopathy
Jakob Triebel 1 , Aura Ileana Moreno-Vega 1 , Miguel Vazquez-Membrillo 1 , Renata Garcia-Franco 2 , Yazmín Macotela 1 , Ellery Lopez-Star 2 , Gonzalo Martínez de la Escalera 1 & Carmen Clapp 1
1Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Querétaro, Mexico; 2Instituto Mexicano Oftalmología, Querétaro, Mexico.
With preterm regression of the hyaloid vascular system, the human vitreous becomes devoid of blood vessels and maintains an avascular, transparent state throughout life. However, diseases of the developing and mature retina, such as retinopathy of prematurity or proliferative diabetic retinopathy (PDR), often result in the invasion of blood vessels into the vitreous, with a risk of causing vitreous hemorrhage, retinal detachment and, consequently, loss of vision or blindness. Here, we investigated the role of vasoinhibins (Vi), antiangiogenic peptides derived from prolactin (PRL) by proteolytic cleavage, as natural inhibitors of angiogenesis in the vitreous. We demonstrate that incubation of PRL with human vitreous resulted in its cleavage to Vi in a time- and vitreous protein concentration-dependent manner. Further, we found that PRL cleavage was prevented by the matrix metalloproteinase (MMP) inhibitors galardin, phenanthroline, and EDTA. The vitreous from patients with PDR showed reduced PRL cleavage and higher proangiogenic effects in an endothelial cell proliferation assay relative to the control vitreous from non-diabetic patients. Control vitreous inhibited endothelial cell proliferation, and immunodepletion of Vi eliminated the anti-proliferative effect, indicating that Vi contribute substantially to the anti-angiogenic action. The presence of PRL in the vitreous was confirmed by an electrochemiluminescence immunoassay, and of Vi, and MMPs by western blotting. We conclude that Vi, generated by MMP-induced PRL cleavage, serve as vitreal inhibitors of angiogenesis and that their generation is impaired in patients with PDR.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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