Fevereiro-Martins Mariza, Guimarães Hercília, Marques-Neves Carlos, Bicho Manuel
Laboratório de Genética and Grupo Ecogenética e Saúde Humana, Instituto de Saúde Ambiental, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, Piso 1C, 1649-028, Lisboa, Portugal.
Instituto de Investigação Científica Bento da Rocha Cabral, Calçada Bento da Rocha Cabral 14, 1250-012, Lisboa, Portugal.
Mol Cell Biochem. 2022 Jun;477(6):1739-1763. doi: 10.1007/s11010-022-04394-4. Epub 2022 Mar 9.
Retinopathy of prematurity (ROP) is a retinal vasoproliferative disorder that represents an important cause of childhood visual impairment and blindness. Although oxidative stress has long been implicated in ROP etiology, other prenatal and perinatal factors are also involved. This review focuses on current research involving inflammation and genetic factors in the pathogenesis of ROP. Increasing evidence suggests that perinatal inflammation or infection contributes to ROP pathogenesis. Cytokines and chemokines with a fundamental role in inflammatory responses and that significantly contributing to angiogenesis are analyzed. Microglia cells, the retinal-resident macrophages, are crucial for retinal homeostasis, however, under sustained pathological stimuli release exaggerated amounts of inflammatory mediators and can promote pathological neovascularization. Current modulation of angiogenic cytokines, such as treatment with antibodies to vascular endothelial growth factor (anti-VEGF), has shown efficacy in the treatment of ocular neovascularization; however, some patients are refractory to anti-VEGF agents, suggesting that other angiogenic or anti-angiogenic cytokines need to be identified. Much evidence suggests that genetic factors contribute to the phenotypic variability of ROP. Several studies have implicated the involvement of candidate genes from different signaling pathways in the development of ROP. However, a genetic component with a major impact on ROP has not yet been discovered. Most studies have limitations and did not replicate results. Future research involving bioinformatics, genomics, and proteomics may contribute to finding more genes associated with ROP and may allow discovering better solutions in the management and treatment of ROP.
早产儿视网膜病变（ROP）是一种视网膜血管增生性疾病，是儿童视力损害和失明的重要原因。虽然氧化应激长期以来一直被认为与ROP的病因有关，但其他产前和围产期因素也参与其中。本综述重点关注目前关于ROP发病机制中炎症和遗传因素的研究。越来越多的证据表明，围产期炎症或感染会导致ROP发病。分析了在炎症反应中起重要作用且对血管生成有显著贡献的细胞因子和趋化因子。小胶质细胞是视网膜驻留巨噬细胞，对视网膜稳态至关重要，然而，在持续的病理刺激下，它们会释放过量的炎症介质，并可促进病理性新生血管形成。目前对血管生成细胞因子的调节，如用血管内皮生长因子抗体（抗VEGF）治疗，已显示出对眼部新生血管形成的治疗效果；然而，一些患者对抗VEGF药物难治，这表明需要识别其他血管生成或抗血管生成细胞因子。许多证据表明，遗传因素导致了ROP的表型变异。几项研究表明，来自不同信号通路的候选基因参与了ROP的发展。然而，尚未发现对ROP有重大影响的遗传成分。大多数研究都有局限性，且结果未能重复。未来涉及生物信息学、基因组学和蛋白质组学的研究可能有助于发现更多与ROP相关的基因，并可能找到更好的ROP管理和治疗解决方案。
