In adults with treated systemic hypertension, retinal capillary density reduced with higher BP and poorer eGFR. These findings highlight the potential role of OCT-A to study early microvascular changes because of systemic hypertension.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
Abstracts Background The retina and brain share many neuronal and vasculature characteristics. We investigated the retinal microvasculature in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) using optical coherence tomography angiography (OCTA). Methods In this cross-sectional study, 24 AD participants, 37 MCI participants, and 29 controls were diagnosed according to internationally accepted criteria. OCTA images of the superficial and deep capillary plexus (SCP, DCP) of the retinal microvasculature were obtained using a commercial OCTA system (Zeiss Cirrus HD-5000 with AngioPlex, Carl Zeiss Meditec, Dublin, CA). The main outcome measures were vessel density (VD) and fractal dimension (FD) in the SCP and DCP within a 2.5-mm ring around the fovea which were compared between groups. Perfusion density of large vessels and foveal avascular zone (FAZ) area were additional outcome parameters. Results Age, gender, and race did not differ among groups. However, there was a significant difference in diabetes status (P = 0.039) and systolic blood pressure (P = 0.008) among the groups. After adjusting for confounders, AD participants showed significantly decreased VD in SCP and DCP (P = 0.006 and P = 0.015, respectively) and decreased FD in SCP (P = 0.006), compared to controls. MCI participants showed significantly decreased VD and FD only in SCP (P = 0.006 and P < 0.001, respectively) and not the DCP (P > 0.05) compared with controls. There was no difference in the OCTA variables between AD and MCI (P > 0.05). Perfusion density of large vessels and FAZ area did not differ significantly between groups (P > 0.05). Conclusions and relevance Eyes of patients with AD have significantly reduced macular VD in both plexuses whereas MCI participants only showed reduction in the superficial plexus. Changes in the retinal microvasculature and capillary network may offer a valuable insight on the brain in AD.
A major complication of hypertension is microvascular damage and capillary rarefaction is a known complication of hypertensive end-organ damage which confers a higher risk of systemic disease such as stroke and cardiovascular events. Our aim was to study the effect of hypertension on the retinal microvasculature using non-invasive optical coherence tomography angiography (octA). We performed a case-control study of 94 eyes of 94 participants with systemic hypertension and 46 normal control eyes from the Singapore chinese eye Study using a standardized protocol to collect data on past medical history of hypertension, including the number and type of hypertensive medications and assessed mean arterial pressure. Retinal vascular parameters were measured in all eyes using octA. in the multivariate analysis adjusting for confounders, compared to controls, eyes of hypertensive patients showed a decrease in the macular vessel density at the level of the superficial [OR 0.02; 95% CI, 0 to 0.64; P 0.027] and deep venous plexuses [OR 0.03; 95% CI, 0 to 0.41; P 0.009] and an increase in the deep foveal avascular zone. this shows that hypertension is associated with reduced retinal vessel density and an increased foveal avascular zone, especially in the deep venous plexus, as seen on octA and there is a potential role in using octA as a clinical tool to monitor hypertensive damage and identifying at risk patients Hypertension is a major cause of morbidity and mortality globally 1,2 , affecting 29.2% men and 24.8% women in 2012 3. A major complication of hypertension is microvascular damage, related partly to abnormal vasomotor tone and increased wall-to-lumen ratio in relation to higher blood pressure 4,5. It has also been suggested that vascular rarefaction may due to either functional alterations such as microvessel constriction resulting in non-perfusion or anatomical alterations resulting in actual non-perfusion and vessel loss 4. There have been many previous studies on the association between hypertension and retinal vasculature. Retinal fundus photo changes seen in response to hypertension include classic hypertensive retinopathy signs such as arteriovenous (AV) nicking, generalized or focal arteriolar narrowing, microaneurysms, intraretinal hemorrhages, cotton wool spots and papilloedema 6. These changes have been shown to confer a higher risk of systemic disease such as stroke and cardiovascular events 6-9. Other studies have also looked at larger retinal vessels (200-300 µm) using color fundus photos and demonstrated a correlation between narrower arteriolar diameter in hypertension 10-13. The impact of hypertension on capillary microvasculature is less clear. Historically, invasive fundus fluorescein angiography (FFA) was needed to evaluate perfusion and the structure of capillary microvasculature. Previous studies using FFA have shown that in patients with hypertension, there is an increase in perifoveal inter-capillary area and decrease in capillary blood velocity 14. However, FFA is not suitable for use in larg...
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused the global pandemic of the Coronavirus disease in late 2019 (COVID-19). Vaccine development efforts have predominantly been aimed at ‘Extra-viral’ Spike (S) protein as vaccine vehicles but there are concerns regarding ‘viral immune escape’ since multiple mutations may enable the mutated virus strains to escape from immunity against S protein. The ‘Intra-viral’ Nucleocapsid (N-protein) is relatively conserved among mutant strains of coronaviruses during spread and evolution. Herein, we demonstrate novel vaccine candidates against SARS-CoV-2 by using the whole conserved N-protein or its fragment/peptides. Using ELISA assay, we showed that high titers of specific anti-N antibodies (IgG, IgG1, IgG2a, IgM) were maintained for a reasonably long duration (> 5 months), suggesting that N-protein is an excellent immunogen to stimulate host immune system and robust B cell activation. We synthesized 3 peptides located at the conserved regions of N-protein among CoVs. One peptide showed as a good immunogen for vaccination as well. Cytokine arrays on post-vaccination mouse sera showed progressive upregulation of various cytokines such as IFN-γ and CCL5, suggesting that TH1 associated responses are also stimulated. Furthermore, vaccinated mice exhibited an elevated memory T cells population. Here, we propose an unconventional vaccine strategy targeting the conserved N-protein as an alternative vaccine target for coronaviruses. Moreover, we generated a mouse monoclonal antibody specifically against an epitope shared between SARS-CoV and SARS-CoV-2, and we are currently developing the First-in-Class humanized anti-N-protein antibody to potentially treat patients infected by various CoVs in the future.
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