Abstract
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.
Highlights
Retinal and choroidal neovascularization are the leading causes of visual impairment in various ocular pathologies, including retinal vein occlusion, age-related macular-degeneration, retinopathy of prematurity and diabetic retinopathy (DR).DR is one of the main complications of diabetes mellitus and it represents the major cause of vision loss in the working-age population [1]
As described in this review, recent experimental evidence has shown that the vitreous obtained from proliferative diabetic retinopathy (PDR) patients elicits angiogenic and inflammatory responses when delivered on the top of the chorioallantoic membrane (CAM)
Despite the fact the PDR vitreous samples are collected after pars plana vitrectomy at the end stage of the disease, when no other therapeutic innervations are available, individual samples are characterized by a highly variable biological effect when tested in the CAM assay
Summary
Retinal and choroidal neovascularization are the leading causes of visual impairment in various ocular pathologies, including retinal vein occlusion, age-related macular-degeneration, retinopathy of prematurity and diabetic retinopathy (DR). A large percentage of patients do not respond to anti-VEGF drugs or exhibit a poor response This limited efficacy may depend on the activation of other pathways promoting ocular angiogenesis as a consequence of the local production of various pro-angiogenic and proinflammatory factors [reviewed in [15,16,17]]. A better understanding of their role in the disease could allow for the identification of novel anti-inflammatory approaches targeting retinal angiogenesis In this frame, the implementation of new methods that could allow the discovery of novel strategies targeting molecular pathways involved in ocular neovascularization is essential. This review highlights the use of the CAM as a model system for the study of the cross talk between angiogenesis and inflammation in PDR and for the screening of anti-angiogenic/anti-inflammatory molecules to be employed for the treatment of angiogenesis-dependent eye diseases
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