Abstract: Ocular vessel networks develop in a highly stereotyped fashion. Abnormal ocular angiogenesis is associated with major diseases including age-related macular degeneration and diabetic retinopathy. Better understanding of mechanisms driving angiogenesis is expected to uncover novel targets to prevent vision loss. Capillary growth is driven by endothelial tip cells, which are selected by dynamic interplay between VEGF, Notch and BMP signaling, with VEGF acting as a positive regulator, and Notch and the BMP receptor Alk1 acting as negative regulators of tip cell formation. The concerted interplay between these molecules ensures that appropriate tip cell numbers leading new vessel branches are formed. In addition, guidance receptors including Neuropilins and Roundabout receptors contribute to vascular patterning by regulating VEGF and BMP signaling. Possibilities to target these pathways during pathological ocular neovascularization will be discussed.
Background: Retinopathy of prematurity (ROP) is considered as the most common reason for blindness in children, particularly in preterm infants. The disease is characterized by the dysregulation of angiogenic mechanisms due to preterm birth, leading ultimately to vascular abnormalities and pathological neovascularization (NV). Retinal detachment and vision loss could represent a concrete risk connected to the most severe forms of ROP, also characterized by inflammation and retinal cell death.
Methods: During the last decades, many animal models of oxygen-induced retinopathy (OIR) have been recognized as useful tools to study the mechanisms of disease, since they reproduce the hallmarks typical of human ROP. Indeed, modulation of retinal vascular development by exposure to different oxygen protocols is possible in these animals, reproducing the main pathological phenotypes of the disease. The easy quantification of abnormal NV and the possibility to perform electrophysiologic, histological and molecular analyses on these models, make OIR animals a fundamental instrument in studying the pathophysiology of ROP and the effects of novel treatments against the disease.
Discussion: Here, the most commonly used OIR protocols in rodents, such as mice and rats, are described as well as the main pathological outcomes typical of these models. Despite their limitations and variables which should be considered whilst using these models, OIR models display several characteristics which have also been confirmed in human patients, validating the usefulness of such animals in the pre-clinical research of ROP.
