Abstract
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.
Highlights
In our previous study [29], we investigated whether elevated Hcy acts directly on retinal pigment pigment epithelium epithelium (RPE) structure and function leading to the development of age-related macular degeneration (AMD)-like features
We found increased immunostaining of CCAAT-enhancer-binding protein homologous protein (CHOP), a transcription factor involved in endoplasmic reticulum (ER) stress-induced apoptosis in retinal nerve fiber layer, ganglion cells, and inner nuclear layer accompanied by elevated levels of apoptotic markers (PARP and cleaved caspase-3) in the retinas of cbs−/− mice, suggesting implication of ER stress/apoptosis in the neuro-vasculopathy associated with the HHcy-linked retinal disease [71]
Our studies suggested oxidative stress is a potential player in Hcy-induced retinal endothelial increase of FITC dextran leakage in human retinal endothelial cells (HRECs) was abolished by co-treatment with the antioxidant Nhyperpermeability and dysfunction [21]
Summary
Homocysteine (Hcy) is a sulfur-containing amino acid that is produced in the body by demethylation of the essential amino acid methionine, which is found mainly in red meat and dairy products. The first pathway (Remethylation pathway) is the main pathway for Hcy metabolism and occurs when methionine level is low. In addition to the reported Hcy-lowering efficacy with B vitamins, omega-3 polyunsaturated polyunsaturated fatty acids (n-3 PUFAs) have gained attention as a class of nutrients with a fatty acids (n-3 PUFAs) have gained attention as a class of nutrients with a possible protective possible protective effect on HHcy-induced cardiovascular injury [12]. Frequent genetic abnormality [18]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
