Retinopathy of prematurity: A review of pathophysiology and signaling pathways

Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina and a leading cause of visual impairment and childhood blindness worldwide. The disease is character-ized by an early stage of retinal microvascular degeneration, followed by neovascularization that can lead to subsequent retinal detachment and permanent visual loss. Several factors play a key role during the different pathological stages of the disease. Oxidative and ni-trosative stress and inflammatory processes are important contributors to the early stage of ROP. Nitric oxide synthase and arginase play important roles in ischemia/reperfusion-induced neurovascular degeneration. Destructive neovascularization is driven by mediators of the hypoxia-inducible factor pathway, such as vascular endothelial growth factor and metabolic factors (succinate). The extracellular matrix is involved in hypoxia-induced reti-nal neovascularization. Vasorepulsive molecules (semaphorin 3A) intervene preventing the revascularization of the avascular zone. This review focuses on current concepts about sig-naling pathways and their mediators, involved in the pathogenesis of ROP, highlighting new potentially preventive and therapeutic modalities. A better understanding of the intricate molecular mechanisms underlying the pathogenesis of ROP should allow the development of more effective and targeted therapeutic agents to reduce aberrant vasoproliferation and facilitate physiological retinal vascular development.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina that leads to visual impairment and childhood blindness worldwide. The disease involves retinal microvascular degeneration, neovascularization, and potential retinal detachment. Oxidative and nitrosative stress, inflammatory processes, as well as nitric oxide synthase and arginase, play important roles in ROP progression. Mediators like vascular endothelial growth factor and succinate contribute to neovascularization, while extracellular matrix and vasorepulsive molecules like semaphorin 3A are involved in the pathogenesis. This article highlights the signaling pathways and molecular mediators of ROP, aiming to develop preventive and therapeutic strategies.