Correlation between choriocapillaris density and retinal sensitivity in age-related macular degeneration

Purpose: The purpose of this study was to investigate the relationship between perfusion of the choriocapillaris (CC) and retinal sensitivity in eyes with intermediate agerelated macular degeneration (iAMD). Methods: This prospective study included patients with iAMD and healthy controls. All enrolled subjects underwent optical coherence tomography angiography (OCT-A) in order to compute the percent perfused choriocapillaris area (PPCA). In patients with iAMD, microperimetry (MP) testing was performed in order to quantify: mean retinal sensitivity (MRS), over an area of 10 degrees; mean macular sensitivity (MMS), over the macular area scanned with OCT-A; and retinal sensitivity (RS) in each macular point. Results: Eighteen eyes of 13 patients were included in the analysis. In addition, 18 eyes of 12 healthy subjects were enrolled as controls. No statistically significant difference (P value > 0.2) was observed in age between patients (73.9 ± 2.0 years) and controls (70.1 ± 2.8 years). We observed significantly lower values of PPCA between patients with iAMD and healthy controls (42.0% ± 3.8% vs. 66.4% ± 3.0%; -Β = 23.8%; P value < 0.001). Among iAMD eyes, higher values of PPCA were significantly associated with higher values of MRS (P value=0.002) and MMS (P value=0.013). Finally, higher values of RS in eachmacular point analyzedwithMPwere significantly (P value<0.001) associated with higher values of PPCA computed in circular regions of interest (ROIs) centered in each analyzed MP point with radii of 0.5 degrees and 1.0 degree. Conclusions: Using OCT-A, we demonstrated a significant association between CC impairment and macular dysfunction, quantified by MP, in iAMD eyes. Translational Relevance: OCT-A could be a useful tool for detecting CC alterations and to monitor disease progression

Why stem/progenitor cells lose their regenerative potential

Nowadays, it is clear that adult stem cells, also called as tissue stem cells, play a central role to repair and maintain the tissue in which they reside by their selfrenewal ability and capacity of differentiating into distinct and specialized cells. As stem cells age, their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired. From a molecular perspective, these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration (i.e epigenomic profile) as well as changes in the tissue microenviroment, both into the niche and by systemic circulating factors. Strikingly, it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various agingassociated disorders. Therefore, understanding how resident stem cell age and affects near and distant tissues is fundamental. Here, we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number, function and phenotype that determine the loss of tissue renewal properties. Furthermore, we examine the possible cell rejuvenation strategies. Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases

Activation of melanocortin receptors MC1 and MC5 attenuates retinal damage in experimental diabetic retinopathy

We hypothesize that melanocortin receptors (MC) could activate tissue protective circuit in a model of streptozotocin- (STZ-) induced diabetic retinopathy (DR) in mice. At 12–16 weeks after diabetes induction, fluorescein angiography (FAG) revealed an approximate incidence of 80% microvascular changes, typical of DR, in the animals, without signs of vascular leakage. Occludin progressively decreased in the retina of mice developing retinopathy. qPCR of murine retina revealed expression of two MC receptors, Mc1r and Mc5r. The intravitreal injection (5 \u1d707L) of the selective MC1 small molecule agonist BMS-470539 (33 \u1d707mol) and the MC5 peptidomimetic agonist PG-901 (7.32 nM) elicited significant protection with regular course and caliber of retinal vessels, as quantified at weeks 12 and 16 after diabetes induction. Mouse retina homogenate settings indicated an augmented release of IL-1\u1d6fc, IL-1\u1d6fd, IL-6, MIP-1\u1d6fc, MIP-2\u1d6fc, MIP-3\u1d6fc, and VEGF from diabetic compared to nondiabetic mice. Application of PG20N or AGRP and MC5 and MC1 antagonist, respectively, augmented the release of cytokines, while the agonists BMS-470539 and PG-901 almost restored normal pattern of these mediators back to nondiabetic values. Similar changes were quantified with respect to Ki-67 staining. Finally, application of MC3-MC4 agonist/antagonists resulted to be inactive with respect to all parameters under assessment

Severe acute respiratory syndrome coronavirus 2 may exploit human transcription factors involved in retinoic acid and interferon-mediated response: a hypothesis supported by an in silico analysis

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19), resulting in acute respiratory disease, is a worldwide emergency. Because recently it has been found that SARS-CoV is dependent on host transcription factors (TF) to express the viral genes, efforts are required to understand the molecular interplay between virus and host response. By bioinformatic analysis, we investigated human TF that can bind the SARS-CoV-2 sequence and can be involved in viral transcription. In particular, we analysed the key role of TF involved in interferon (IFN) response. We found that several TF could be induced by the IFN antiviral response, specifically some induced by IFN-stimulated gene factor 3 (ISGF3) and by unphosphorylated ISGF3, which were found to promote the transcription of several viral open reading frame. Moreover, we found 22 TF binding sites present only in the sequence of virus infecting humans but not bat coronavirus RaTG13. The 22 TF are involved in IFN, retinoic acid signalling and regulation of transcription by RNA polymerase II, thus facilitating its own replication cycle. This mechanism, by competition, may steal the human TF involved in these processes, explaining SARS-CoV-2's disruption of IFN-I signalling in host cells and the mechanism of the SARS retinoic acid depletion syndrome leading to the cytokine storm. We identified three TF binding sites present exclusively in the Brazilian SARS-CoV-2 P.1 variant that may explain the higher severity of the respiratory syndrome. These data shed light on SARS-CoV-2 dependence from the host transcription machinery associated with IFN response and strengthen our knowledge of the virus's transcription and replicative activity, thus paving the way for new targets for drug design and therapeutic approaches

Higher reliability of 18F-FDG target background ratio compared to standardized uptake value in vulnerable carotid plaque detection: a pilot study.

Objective: To evaluate the role of [18F]-fluorodeoxyglucose positron emission tomography/computer tomography [18F-FDG PET/CT] comparing target background ratio (TBR) and standardized uptake value (SUV) with the histopathological inflammatory status of the carotid plaques. Background: Vulnerable carotid plaques are the primary cause of acute cerebrovascular events. 18F-FDG PET/CT represents a morpho-functional technique able to identify the highly inflamed and most vulnerable carotid plaques. Several literature studies experimented this new method to identify vascular inflammation, but few have effectively compared PET/CT results with plaque histological data and no studies had directly compared TBR to SUV. Methods: Thirty-two consecutive patients (20 men and 12 women, mean age 74 ± 8 years) undergoing carotid endarterectomy were enrolled and studied with carotid 18F-FDG PET/CT. Maximum and mean SUV and TBR were used to quantify 18F-FDG uptake while surgical specimens were analyzed by optical microscopy to identify inflamed carotid plaques, with evaluation of macrophages infiltration by mean of immunohistochemistry. On the basis of the presence of inflammation at the histological analysis, we divided population in two groups: group A (n = 12) patients with inflamed carotid plaques and group B (n = 20) patients with non-inflamed ones, then crossed and evaluated the histological data with 18F-FDG PET/CT findings. Results: SUV max and SUV mean values resulted higher in group A (respectively, 2.14 ± 0.77 and 1.99 ± 0.68) than in group B (respectively, 1.79 ± 0.37 and 1.64 ± 0.34) without reaching a statistical significance (p = ns). TBR max and TBR mean values resulted higher in group A (respectively, 1.42 ± 0.32 and 1.34 ± 0.26) than in group B (respectively, 1.16 ± 0.19 and 1.03 ± 0.20) with a statistically significant differences between the two groups and carotid inflammation (respectively, p < 0.01 and p < 0.001). Conclusion: TBR (max and mean values) is a more reliable parameter than SUV in identifying inflamed plaques. Although limited by the small population analyzed, our results suggest the important role of 18F-FDG PET/CT, using TBR, in identification of high-risk carotid atherosclerotic plaques. © 2014 The Japanese Society of Nuclear Medicine

Endothelial dysfunction and renal fibrosis in endotoxemia-induced oliguric kidney injury: possible role of LPS binding protein

The pathophysiology of endotoxemia-induced acute kidney injury (AKI) is characterized by an intense activation of the host immune system and renal resident cells by lipopolysaccharide (LPS) and derived proinflammatory products. However, the occurrence of renal fibrosis in this setting has been poorly investigated. The aim of the present study was to investigate the possible association between endothelial dysfunction and acute development of tissue fibrosis in a swine model of LPS-induced AKI. Moreover, we studied the possible effects of coupled plasma filtration adsorption (CPFA) in this setting