Elevated plasma homocysteine (Hcy) level, known as hyperhomocysteinemia (HHcy) has been linked to different systemic and neurological diseases, well-known as a risk factor for systemic atherosclerosis and cardiovascular disease (CVD) and has been identified as a risk factor for several ocular disorders, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). Different mechanisms have been proposed to explain HHcy-induced visual dysfunction, including oxidative stress, upregulation of inflammatory mediators, retinal ganglion cell apoptosis, and extracellular matrix remodeling. Our previous studies using in vivo and in vitro models of HHcy have demonstrated that Hcy impairs the function of both inner and outer blood retinal barrier (BRB). Dysfunction of BRB is a hallmark of vision loss in DR and AMD. Our findings highlighted oxidative stress, ER stress, inflammation, and epigenetic modifications as possible mechanisms of HHcy-induced BRB dysfunction. In addition, we recently reported HHcy-induced brain inflammation as a mechanism of blood–brain barrier (BBB) dysfunction and pathogenesis of Alzheimer’s disease (AD). Moreover, we are currently investigating the activation of glutamate receptor N-methyl-d-aspartate receptor (NMDAR) as the molecular mechanism for HHcy-induced BRB dysfunction. This review focuses on the studied effects of HHcy on BRB and the controversial role of HHcy in the pathogenesis of aging neurological diseases such as DR, AMD, and AD. We also highlight the possible mechanisms for such deleterious effects of HHcy.

中文翻译：

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高同型半胱氨酸血症对血视网膜屏障 (BRB) 功能障碍的影响。

升高的血浆同型半胱氨酸 (Hcy) 水平，即高同型半胱氨酸血症 (HHcy) 与不同的全身和神经系统疾病有关，是众所周知的全身性动脉粥样硬化和心血管疾病 (CVD) 的危险因素，并已被确定为多种疾病的危险因素。眼部疾病，例如糖尿病视网膜病变 (DR) 和年龄相关性黄斑变性 (AMD)。已经提出了不同的机制来解释 HHcy 诱导的视觉功能障碍，包括氧化应激、炎症介质的上调、视网膜神经节细胞凋亡和细胞外基质重塑。我们之前使用 HHcy 体内和体外模型进行的研究表明，Hcy 会损害内部和外部血液视网膜屏障 (BRB) 的功能。BRB 功能障碍是 DR 和 AMD 视力丧失的标志。我们的研究结果强调氧化应激、ER 应激、炎症和表观遗传修饰是 HHcy 诱导的 BRB 功能障碍的可能机制。此外，我们最近报道了 HHcy 诱导的脑炎症是血脑屏障 (BBB) 功能障碍和阿尔茨海默病 (AD) 发病机制的一种机制。此外，我们目前正在研究谷氨酸受体的激活Ñ甲基d天冬氨酸受体（NMDAR）作为血症诱发的BRB功能障碍的分子机制。本综述重点研究了 HHcy 对 BRB 的影响，以及 HHcy 在 DR、AMD 和 AD 等衰老神经疾病发病机制中的有争议的作用。我们还强调了 HHcy 的这种有害影响的可能机制。