Retinopathy of Prematurity and Glaucoma: possible strategies to prevent Neovascularization and Neurodegeneration

A variety of pathological processes can disrupt the sophisticated and delicate retina architecture, leading to a broad-spectrum of vision-threatening diseases. Retinopathy of prematurity (ROP) is a multifactorial neovascular disease which causes perturbation of the physiological vascular development in the retina of preterm infants, often leading to blindness. ROP progresses in two phases. Of them, the second hypoxic-proliferative phase causes pathological hyper-vascularisation in the superficial plexus, causing functional impairments. Vascular endothelial growth factor (VEGF) plays a crucial role in promoting angiogenesis, both in physiological and in pathological conditions. A growing body of evidence is progressively highlighting the involvement of β-adrenoceptors (BAR) in VEGF production and retinal neovascularization. Another pathological condition able to alter retinal architecture is glaucoma. Indeed, although the term glaucoma refers to a group of lifelong progressive optic neuropathies that differ cause, risk factors, demographics, symptoms, duration, treatment, and prognosis, the common features of all glaucoma forms are excavation (cupping) of the optic disc, apoptotic degeneration of retinal ganglion cells (RGC) and thinning of the nerve fibre layer (NFL). Glaucoma is the leading cause of irreversible blindness worldwide. Here, we investigated the effects of hypoxia on BAR expression using human Müller cells, the major source of retinal VEGF and human retinal endothelial cells, the main receivers of VEGF within the retina. Subsequently, we tested the effects of BAR3 antagonism in hypoxic condition and/or nitric oxide synthase induction/blocking on VEGF production. We also evaluated the effects of BAR3 agonism/antagonism and BAR2 agonism in a murine model of oxygen-induced retinopathy (OIR) widely used to study ROP. Then, we used a murine model of induced high-tension glaucoma to investigate the putative beneficial effects of an Achebuche (ACE) oil enriched diet against the deleterious consequences of glaucoma. In particular, within the retina of the model, we evaluated glia reactivity, the inflammatory status, the oxidative stress markers expression, the ischemic damage, the apoptosis activation, and RGC functionality.