Angiogenesis-Inflammation Cross Talk in Diabetic Retinopathy: Novel Insights From the Chick Embryo Chorioallantoic Membrane/Human Vitreous Platform

Pathological angiogenesis of the retina is a key component of irreversible causes of
blindness, as observed in proliferative diabetic retinopathy (PDR). The pathogenesis of
PDR is complex and involves vascular, inflammatory, and neuronal mechanisms. Several
structural and molecular alterations associated to PDR are related to the presence of
inflammation that appears to play a non-redundant role in the neovascular response
that characterizes the retina of PDR patients. Vascular endothelial growth factor (VEGF)
blockers have evolved over time for the treatment of retinal neovascularization. However,
several limitations to anti-VEGF interventions exist. Indeed, the production of other
angiogenic factors and pro-inflammatory mediators may nullify and/or cause resistance
to anti-VEGF therapies. Thus, appropriate experimental models are crucial for dissecting
the mechanisms leading to retinal neovascularization and for the discovery of more
efficacious anti-angiogenic/anti-inflammatory therapies for PDR patients. This review
focuses on the tight cross talk between angiogenesis and inflammation during PDR and
describe how the chick embryo chorioallantoic membrane (CAM) assay may represent a
cost-effective and rapid in vivo tool for the study of the relationship between neovascular
and inflammatory responses elicited by the vitreous humor of PDR patients and for the
screening of novel therapeutic agents.