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Inflammation and elevated expression of high temperature requirement A serine peptidase 1 (HTRA1) are known high risk factors for age-related macular degeneration (AMD). However, the specific mechanism that HTRA1 causes AMD and the relationship between HTRA1 and inflammation remains unclear. We found that lipopolysaccharide (LPS) induced inflammation enhanced the expression of HTRA1, NF-κB, and p-p65 in ARPE-19 cells. Overexpression of HTRA1 up-regulated NF-κB expression, and on the other hand knockdown of HTRA1 down-regulated the expression of NF-κB. Moreover, NF-κB siRNA has no significant effect on the expression of HTRA1, suggesting HTRA1 works upstream of NF-κB. These results demonstrated that HTRA1 plays a pivotal role in inflammation, explaining possible mechanism of overexpressed HTRA1-induced AMD. Celastrol, a very common anti-inflammatory and antioxidant drug, was found to suppress inflammation by inhibiting phosphorylation of p65 protein efficaciously in RPE cells, which may be applied to the therapy of age-related macular degeneration.

This study examined the construct validity of the Adult OMNI Perceived Exertion Scale for Resistance Exercise (OMNI-RES). Forty (20 men and 20 women) subjects performed 1 repetition of the knee extension exercise at 40, 50, 60, 70, 80, and 90% of the 1 repetition maximum. Active muscle and overall body ratings of perceived exertion (RPE) were collected from the Borg 15-category RPE scale and the OMNI-RES immediately following each repetition. Construct validity was established by correlating RPE from the OMNI-RES with RPE from the Borg RPE scale using regression analysis. The results indicated a positive and linear relationship between RPE from the OMNI-RES and RPE from the Borg scale for both men and women. Validity coefficients ranged from r = 0.94 to 0.97. The high level of construct validity indicates that the OMNI-RES measures the same properties of exertion as the Borg RPE scale during resistance exercise and suggests that the 2 scales can be used interchangeably during resistance exercise.

Best Vitelliform Macular dystrophy (BVMD) is the most prevalent of the distinctive retinal dystrophies caused by mutations in the BEST1 gene. This gene, which encodes for a homopentameric calcium-activated ion channel, is crucial for the homeostasis and function of the retinal pigment epithelia (RPE), the cell type responsible for recycling the visual pigments generated by photoreceptor cells. In BVMD patients, mutations in this gene induce functional problems in the RPE cell layer with an accumulation of lipofucsin that evolves into cell death and loss of sight. In this work, we employ iPSC-RPE cells derived from a patient with the p.Pro77Ser dominant mutation to determine the correlation between this variant and the ocular phenotype. To this purpose, gene and protein expression and localization are evaluated in iPSC-RPE cells along with functional assays like phagocytosis and anion channel activity. Our cell model shows no differences in gene expression, protein expression/localization, or phagocytosis capacity, but presents an increased chloride entrance, indicating that the p.Pro77Ser variant might be a gain-of-function mutation. We hypothesize that this variant disturbs the neck region of the BEST1 channel, affecting channel function but maintaining cell homeostasis in the short term. This data shed new light on the different phenotypes of dominant mutations in BEST1, and emphasize the importance of understanding its molecular mechanisms. Furthermore, the data widen the knowledge of this pathology and open the door for a better diagnosis and prognosis of the disease.

Retinal pigment epithelial (RPE) cells maintain the health and functional integrity of both photoreceptors and the choroidal vasculature. Loss of RPE differentiation has long been known to play a critical role in numerous retinal diseases, including inherited rod-cone degenerations, inherited macular degeneration, age-related macular degeneration, and proliferative vitreoretinopathy. Recent studies in post-mortem eyes have found upregulation of critical epithelial-mesenchymal transition (EMT) drivers such as TGF-β, Wnt, and Hippo. As RPE cells become less differentiated, they begin to exhibit the defining characteristics of mesenchymal cells, namely, the capacity to migrate and proliferate. A number of preclinical studies, including animal and cell culture experiments, also have shown that RPE cells undergo EMT. Taken together, these data suggest that RPE cells retain the reprogramming capacity to move along a continuum between polarized epithelial cells and mesenchymal cells. We propose that movement along this continuum toward a mesenchymal phenotype be defined as RPE Dysfunction. Potential mechanisms include impaired tight junctions, accumulation of misfolded proteins and dysregulation of several key pathways and molecules, such as TGF-β pathway, Wnt pathway, nicotinamide, microRNA 204/211 and extracellular vesicles. This review synthesizes the evidence implicating EMT of RPE cells in post-mortem eyes, animal studies, primary RPE, iPSC-RPE and ARPE-19 cell lines.

TRIMP and sRPE are both representative indicators of training load(TL), and the correlation between two has been widely demonstrated across various sports. The aim of this study was to investigate the reliability of sRPE-TRIMP correlation across different intensities/duration of training in cross-country skiing, and whether sRPE can serve as an validity supplement to TRIMP data in cases of lost heart rate data. 10 athletes were used as the experimental objects. The intensity, duration and RPE of 273 different types of training sessions were collected, and statistical methods were used for data analysis. 1. There was a significant correlation between sRPE and TRIMP (  = 0.68,  < 0.05), but the correlation differs among the LIT, MIT and HIT groups (  = 0.70, 0.46, = 0.31,  < 0.05) 2. sRPE-TRIMP correlation among three different time duration in the LIT group (0-60 min, 60-120 min and 120-180 min), are all highly significant (  = 0.70, 0.67, 0.69,  < 0.05) and the LRsRPE-TRIMP of 3 duration have no significant differences (chow test,  > 0.05). 3. The difference in actual training duration between samples was the main reason for the difference in the application effect of sRPE, because the actual training duration ratio of LIT was 89.7 ± 16.4%; MIT, 98.5 ± 6.2%; and HIT, 94.4 ± 13.5%. 1. The linear relationship between sRPE and TRIMP (LRsRPE-TRIMP) is more significant in LIT compared to that in MIT and HIT. 2. Variations in the duration of LIT sessions do not affect the consistency of the relationship between sRPE and TRIMP. 3. Discrepancies between actual and planned training durations directly impact the significance of the LRsRPE-TRIMP.

Retinal pigment epithelium (RPE) is a monolayer of the pigmented cells that lies on the thin extracellular matrix called Bruch’s membrane. This monolayer is the main component of the outer blood–retinal barrier (BRB), which plays a multifunctional role. Due to their crucial roles, the damage of this epithelium causes a wide range of diseases related to retinal degeneration including age-related macular degeneration, retinitis pigmentosa, and Stargardt disease. Unfortunately, there is presently no cure for these diseases. Clinically implantable RPE for humans is under development, and there is no practical examination platform for drug development. Here, we developed porcine Bruch’s membrane-derived bioink (BM-ECM). Compared to conventional laminin, the RPE cells on BM-ECM showed enhanced functionality of RPE. Furthermore, we developed the Bruch’s membrane-mimetic substrate (BMS) via the integration of BM-ECM and 3D printing technology, which revealed structure and extracellular matrix components similar to those of natural Bruch’s membrane. The developed BMS facilitated the appropriate functions of RPE, including barrier and clearance functions, the secretion of anti-angiogenic growth factors, and enzyme formation for phototransduction. Moreover, it could be used as a basement frame for RPE transplantation. We established BMS using 3D printing technology to grow RPE cells with functions that could be used for an in vitro model and RPE transplantation.

To analyze changes in the vertical dimension of the lower third of the face studied on teleradiograph in L-L following rapid palatal expansion achieved by four-band Hyrax-type rapid palatal expander (RPE) and by acrylic-bonded McNamara RPE to identify the most appropriate therapeutic choice based on the patient's facial growth pattern. 30 patients were selected, of whom 20 (9 males and 11 females with a mean age of 8.285 ± 1.216) were treated using McNamara RPE (Group D), and 10 (6 males and 4 females with a mean age of 8.562 ± 1.152) were treated with Hyrax RPE (Group B), for an average treatment time T0-T1 of 0.96 ± 0.501 years. According to Tweed and Ricketts, Cephalometric tracings obtained from lateral cephalograms at T0 and T1 were analyzed to study changes in the vertical dimension of the lower third of the face. For this purpose, 6 cephalometric landmarks were considered: convexity (distance of point A to the NPg plane), Ricketts’ total face height (angle between the NBa plane and Xi-Pm plane), lower face height (angle between the ANS and Xi-Pm planes), facial axis (angle between the NaBa plane and PtGn plane), ANB angle, and FMA angle. No statistically significant differences were found between the measurements at T0 and T1 for any of the 6 cephalometric measurements considered, neither within the single groups nor when comparing the two. However, a greater increasing trend was found for some variables between the two groups, such as Ricketts' total facial height, lower facial height, and FMA angle, although not statistically significant. Hyrax and McNamara's RPEs have provided minimal changes in the vertical component during palatal expansion treatment, thus demonstrating their ability to preserve the vertical dimension of the face. Therefore, there are no contraindications for using either appliance for patients with dolichofacial growth patterns.

Subretinal fibrosis significantly contributes to vision loss in neovascular age‐related macular degeneration (nAMD). Epithelial‐to‐mesenchymal transition (EMT) in RPE cells is a key early step in subretinal fibrosis. While mitochondrial dysfunction in RPE is involved, the metabolic and molecular connections between EMT and mitochondria are not well understood. This study explores the role of oxoglutarate carrier (OGC; Slc25a11) on EMT and investigates the molecular mechanisms, focusing on its role in mitochondrial metabolism and GSH transport. OGC‐silenced or overexpressed ARPE‐19 cells were treated with TGF‐β2 (10 ng/mL) for 48 h. EMT markers, cell migration, mtGSH, and mitochondrial bioenergetics and signaling pathways were assessed. In vivo, subretinal fibrosis was induced in wild‐type and OGC+/− mice via laser photocoagulation. Fibrosis volume was measured using optical coherence tomography and immunostaining in RPE‐choroid flat mounts. OGC silencing aggravated EMT, while overexpression attenuated TGF‐β2‐induced EMT, cell proliferation, and migration. OGC knockdown significantly enhanced RPE EMT, as evidenced by upregulated expression of α‐SMA, fibronectin, collagen type I, and Slug, while E‐cadherin was downregulated. OGC overexpression improved mitochondrial bioenergetics, whereas its inhibition reduced mitochondrial respiration, which was further aggravated by co‐treatment with TGF‐β2. Loss of OGC promoted cell proliferation and migration through Slug‐mediated EMT. OGC depletion stimulated EMT via pSmad2/3 upregulation, dependent on the PI3K/AKT signaling pathway activation. In vivo studies further demonstrate that subretinal fibrosis was significantly augmented in OGC+/− mice via TGF‐β2‐dependent PI3K signaling. In conclusion, modulating OGC expression in RPE affects EMT and mitochondrial function, making OGC a potential therapeutic target for subretinal fibrosis in nAMD. The diagram shows that OGC deficiency leads to mitochondrial dysfunction, which activates the PI3K/AKT/Slug pathway and triggers epithelial‐mesenchymal transition (EMT) in retinal pigment epithelial cells. This process promotes myofibroblast accumulation and subretinal fibrosis in laser‐induced CNV, contributing to the progression of AMD.

The reprogramming of retinal pigment epithelium (RPE) cells into retinal cells (transdifferentiation) lies in the bases of retinal regeneration in several Urodela. The identification of the key genes involved in this process helps with looking for approaches to the prevention and treatment of RPE-related degenerative diseases of the human retina. The purpose of our study was to examine the transcriptome changes at initial stages of RPE cell reprogramming in adult newt Pleurodeles waltl. RPE was isolated from the eye samples of day 0, 4, and 7 after experimental surgical detachment of the neural retina and was used for a de novo transcriptome assembly through the RNA-Seq method. A total of 1019 transcripts corresponding to the differently expressed genes have been revealed in silico: the 83 increased the expression at an early stage, and 168 increased the expression at a late stage of RPE reprogramming. We have identified up-regulation of classical early response genes, chaperones and co-chaperones, genes involved in the regulation of protein biosynthesis, suppressors of oncogenes, and EMT-related genes. We revealed the growth in the proportion of down-regulated ribosomal and translation-associated genes. Our findings contribute to revealing the molecular mechanism of RPE reprogramming in Urodela.