Modrzejewska Monika, Zdanowska Oliwia, Połubiński Piotr
2nd Department of Ophthalmology, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland.
K. Marcinkowski University Hospital in Zielona Góra, 65-046 Zielona Góra, Poland.
J Clin Med. 2024 Jul 10;13(14):4034. doi: 10.3390/jcm13144034.
Hypoxia-inducible factor (HIF) plays a crucial role in regulating oxygen sensing and adaptation at the cellular level, overseeing cellular oxygen homeostasis, erythrocyte production, angiogenesis, and mitochondrial metabolism. The hypoxia-sensitive HIF-1α subunit facilitates tissue adaptation to hypoxic conditions, including the stimulation of proangiogenic factors. Retinopathy of prematurity (ROP) is a proliferative vascular disease of the retina that poses a significant risk to prematurely born children. If untreated, ROP can lead to retinal detachment, severe visual impairment, and even blindness. The pathogenesis of ROP is not fully understood; however, reports suggest that premature birth leads to the exposure of immature ocular tissues to high levels of exogenous oxygen and hyperoxia, which increase the synthesis of reactive oxygen species and inhibit HIF expression. During the ischemic phase, HIF-1α expression is stimulated in the hypoxia-sensitive retina, causing an overproduction of proangiogenic factors and the development of pathological neovascularization. Given the significant role of HIF-1α in the development of ROP, considering it as a potential molecular target for therapeutic strategies appears justified. This review synthesizes information from the last six years (2018-2024) using databases such as PubMed, Google Scholar, and BASE, focusing on the role of HIF-1α in the pathogenesis of ROP and its potential as a target for new therapies.
缺氧诱导因子(HIF)在细胞水平调节氧感知和适应过程中发挥着关键作用,负责监督细胞氧稳态、红细胞生成、血管生成和线粒体代谢。对缺氧敏感的HIF-1α亚基促进组织适应缺氧条件,包括刺激促血管生成因子。早产儿视网膜病变(ROP)是一种视网膜增殖性血管疾病,对早产儿构成重大风险。如果不进行治疗,ROP可导致视网膜脱离、严重视力损害甚至失明。ROP的发病机制尚未完全明确;然而,有报道表明,早产会使未成熟的眼部组织暴露于高水平的外源性氧气和高氧环境中,这会增加活性氧的合成并抑制HIF表达。在缺血阶段,对缺氧敏感的视网膜中HIF-1α表达受到刺激,导致促血管生成因子过度产生和病理性新生血管形成。鉴于HIF-1α在ROP发展过程中的重要作用,将其视为治疗策略的潜在分子靶点似乎是合理的。本综述使用PubMed、谷歌学术和BASE等数据库,综合了过去六年(2018 - 2024年)的信息,重点关注HIF-1α在ROP发病机制中的作用及其作为新疗法靶点的潜力。