AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |
Back to Blog
Miana kassis12/23/2023 We reported retinal pigment epithelial (RPE) function disruption (barrier and phagocytic functions) by HHcy. Besides the cbs (genetic) model of HHcy, we used another model of HHcy by injecting L-Homocysteine thiolactone hydrochloride locally in wild type (B57-BL6) mouse eyes (intravitreal injection) and we were able to confirm the changes we previously observed in the CBS mice. Gliosis is a reactive change in glial cells in response to damage to the central nervous system (CNS) and involves the hypertrophy or proliferation of several different types of glial cells, including astrocytes and microglia. Our previous studies on a mouse model of HHcy caused by deficiency of the cystathionine-β-synthase enzyme (CBS) (cbs −/− and cbs +/− mice) reported an association between HHcy and retinal vascular dysfunction such as pathological neovascularization, central retinal vein occlusion, pericyte loss, and gliosis. However, some potential mechanisms have been suggested for HHcy-induced brain damage and explain the connections between HHcy and AD, such as increasing cellular oxidative stress and hypo-methylation of DNA and proteins ER stress, cerebrovascular damage, neuroinflammation, Aβ elevation, and tau protein phosphorylation. The underlying cellular mechanisms by which elevated Hcy induce neuronal death or exacerbate the consequences of other insults are still unclear. Indeed, HHcy was reported to double the risk of developing AD. Hcy was elevated in patients with AD compared with normal controls and has been suggested as an independent risk factor for AD, to reduce the size and volume of the hippocampus and cortex of healthy elderly people, to sensitize hippocampal neurons to excitotoxins in animal models, to enhance neuronal death in mouse models of cerebral stroke, and to induce a dose-dependent increase in apoptotic cell death in cultured hippocampal neurons. These changes are concomitant with NMDAR activation and oxidative stress, ultimately resulting in AD pathology. AD progression has also been related to a gradual damage in function and structure in the hippocampus and neocortex areas of the brain involved in memory and cognition. In addition, it is associated with BBB dysfunction. The main pathological features of AD are the intracellular accumulation of neurofibrillary tangles composed of hyperphosphorylated tau protein and increased production and deposition of amyloid-β (Aβ) with concomitant loss of synapses and neurons. The etiology of AD is complex and multi-factorial and still poorly understood. The symptoms of this disease may start as simple symptoms, such as early forgetfulness, then deteriorate over time to gradual worsening in language, orientation, and behavior and late severe loss of memory and some bodily functions until eventual death. Unfortunately, there is still no available effective treatment for AD, however, controlling the risk factors can still reduce the number of cases and associated cost, especially as AD is a devastating disease for the patients and their families and puts a huge financial burden on the whole of society. As the population ages, the prevalence of AD is expected to increase to effect over 100 million by 2050. Worldwide, more than 26 million individuals have been diagnosed with AD. Īlzheimer’s disease (AD) is the most common form of neurodegenerative disease and is the major cause of dementia, accounting for 60–70% of cases. Vision is negatively affected in clinical situations associated with BRB breakdown, such as DR, in which the inner BRB is altered, and AMD, in which the outer BRB is altered. The BRB consists of two components, an inner and outer BRB. An intact BRB is vital for retinal structural and functional integrity as it plays an essential role in the maintenance of the retinal neuron microenvironment. Similarly to the BBB, the blood–retinal barrier (BRB) regulates fluids and molecular movement between the ocular vascular and retinal tissues and prevents leakage of macromolecules and other potentially harmful agents into the retina. This barrier is tightly maintained via specialized tight junctions, gap junctions, and adherent junctions and is vital for various features, such as: preventing entry of harmful substances to the neuronal tissue of the brain, performing selective transportation and trafficking of molecules into and out of the brain, and allowing specific ion transporter channels to regulate ionic transporters. The blood–brain barrier (BBB) separates the brain from the circulatory system and is made of tightly packed endothelial cells that line the cerebral vessels, separating blood stream components from the neuronal brain tissue. Our and others’ work reported that HHcy causes disruption of the blood barrier function in both the brain and retina.
0 Comments
Read More
Leave a Reply. |