Frontiers in bioscience (Landmark edition)最新文献

{"title":"The Effects of Dexamethasone on Human Lens Epithelial Cells and the Analysis of Related Pathways with Transcriptome Sequencing.","authors":"Xinjie Shu, Jiamin Gao, Han Xu, Qiyou Li, Yu Gong, Jiawen Li","doi":"10.31083/j.fbl2911391","DOIUrl":"https://doi.org/10.31083/j.fbl2911391","url":null,"abstract":"<p><strong>Background: </strong>The goal of this study was to investigate the effects of dexamethasone on human lens epithelial cells (HLECs) and the potential mechanisms.</p><p><strong>Methods: </strong>HLECs (HLE-B3) were cultured <i>in vitro</i> to assess the effects of dexamethasone on cell size at different concentrations. Immunofluorescence staining was used to detect specific protein expression in HLE-B3 cells. The cell size was observed using phase-contrast microscopy, and the length and area were quantitatively measured with ImageJ software for statistical analysis. Flow cytometry was used to verify these outcomes. The means of three groups were statistically analyzed using one-way analysis of variance, whereas the means of two groups were statistically analyzed with the parametric Student's <i>t</i>-test. Additionally, high-throughput transcriptome sequencing was performed to compare messenger RNA (mRNA) expression levels between different concentrations of dexamethasone treatment groups and the control group, to identify potential signaling pathways. Subsequently, we performed quantitative Polymerase Chain Reaction (qPCR), immunofluorescence staining, and molecular docking experiments on the key differentially expressed genes.</p><p><strong>Results: </strong>Dexamethasone affected the size of HLE-B3 cells. Both 0.25 and 0.5 μmol/L dexamethasone increased cell length and area, exhibiting no significant difference between the two treatment groups. Flow cytometry showed that dexamethasone increased cell size and granularity, with 0.25 μmol/L dexamethasone leading to larger cell areas and higher intracellular granularity. High-throughput transcriptome sequencing revealed significant upregulation of lysophosphatidic acid receptor 1 (LPAR1) and the pathways related to the glucocorticoid (GC) receptor.</p><p><strong>Conclusions: </strong>Certain concentrations of dexamethasone impact the morphology and biological functions of HLECs. As a subtype of G protein-coupled receptors, LPAR1 on the cell membrane may interact with dexamethasone, affecting cell size and inhibiting autophagy via the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. These discoveries offer crucial biological insights into how dexamethasone influences the morphology and function of HLECs and the pathogenesis of GC-induced cataracts, offering potential molecular targets for future therapeutic strategies.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 11","pages":"391"},"PeriodicalIF":3.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signal Transduction Mechanisms of Focal Adhesions: Src and FAK-Mediated Cell Response.","authors":"Kazuo Katoh","doi":"10.31083/j.fbl2911392","DOIUrl":"https://doi.org/10.31083/j.fbl2911392","url":null,"abstract":"<p><p>Cell-to-substrate adhesion sites, also known as focal adhesion sites (FAs), are complexes of different proteins on the cell surface. FAs play important roles in communication between cells and the extracellular matrix (ECM), leading to signal transduction involving different proteins that ultimately produce the cell response. This cell response involves cell adhesion, migration, motility, cell survival, and cell proliferation. The most important component of FAs are integrins. Integrins are transmembrane proteins that receive signals from the ECM and communicate them to the cytoplasm, thus activating several downstream proteins in a signaling cascade. Cellular Proto-oncogene tyrosine-protein kinase Src (c-Src) and focal adhesion kinase (FAK) are non-receptor tyrosine kinases that functionally interact to promote crucial roles in FAs. c-Src is a tyrosine kinase, activated by autophosphorylation and, in turn, activates another important protein, FAK. Activated FAK directly interacts with the cytoplasmic domain of integrin and activates other FA proteins by attaching to them. These proteins activated by FAK then activate other downstream pathways such as mitogen-activated protein kinase (MAPK) and Akt pathways involved in cell proliferation, migration, and cell survival. Src can induce detachment of FAK from the integrin to increase the focal adhesion turnover. As a result, the Src-FAK complex in FAs is critical for cell adhesion and survival mechanisms. Overexpression of FA proteins has been linked to a variety of pathological disorders, including cancers, growth retardation, and bone deformities. FAK and Src are overexpressed in various cancers. This review, which focuses on the roles of two important signaling proteins, c-Src and FAK, attempts to provide a thorough and up-to-date examination of the signal transduction mechanisms mediated by focal adhesions. The author also described that FAK and Src may serve as potential targets for future therapies against diseases associated with their overexpression, such as certain types of cancer.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 11","pages":"392"},"PeriodicalIF":3.3,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding Multiple Sclerosis Pathophysiology and Current Disease-Modifying Therapies: A Review of Unaddressed Aspects.","authors":"Eiman M A Mohammed","doi":"10.31083/j.fbl2911386","DOIUrl":"https://doi.org/10.31083/j.fbl2911386","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is a complex autoimmune disorder of the central nervous system (CNS) with an unknown etiology and pathophysiology that is not completely understood. Although great strides have been made in developing disease-modifying therapies (DMTs) that have significantly improved the quality of life for MS patients, these treatments do not entirely prevent disease progression or relapse. Identifying the unaddressed pathophysiological aspects of MS and developing targeted therapies to fill in these gaps are essential in providing long-term relief for patients. Recent research has uncovered some aspects of MS that remain outside the scope of available DMTs, and as such, yield only limited benefits. Despite most MS pathophysiology being targeted by DMTs, many patients still experience disease progression or relapse, indicating that a more detailed understanding is necessary. Thus, this literature review seeks to explore the known aspects of MS pathophysiology, identify the gaps in present DMTs, and explain why current treatments cannot entirely arrest MS progression.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 11","pages":"386"},"PeriodicalIF":3.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulfated Galactan Derivative from <i>Gracilaria fisheri</i> Improves Histopathology and Alters Wound Healing-Related Proteins in the Skin of Excision Rats.","authors":"Kamonwan Jongsomchai, Arnon Pudgerd, Waraporn Sakaew, Kanokpan Wongprasert, José Kovensky, Tawut Rudtanatip","doi":"10.31083/j.fbl2911388","DOIUrl":"https://doi.org/10.31083/j.fbl2911388","url":null,"abstract":"<p><strong>Background: </strong>The biological activities of sulfated polysaccharides (SP) are well-documented, especially regarding wound healing. Sulfated galactan (SG), a type of SP extracted from the red seaweed <i>Gracilaria fisheri</i>, has been identified as having multiple therapeutic properties related to its wound healing capacity. Recent research indicates that degraded SG (DSG) from <i>G. fisheri</i>, when combined with octanoyl ester (DSGO), can improve wound healing in fibroblasts. However, the effectiveness of natural products in clinical settings often differs from <i>in vitro</i> results. This study aimed to develop and evaluate ointments containing DSG and DSGO for skin repair in an animal model.</p><p><strong>Methods: </strong>Twenty-four Wistar rats were divided into four groups: (1) normal control, (2) ointment control, (3) DSG ointment, and (4) DSGO ointment. After inducing full-thickness excision wounds, these ointments were applied to the wounds. Wound contraction rate, histopathology, and protein related wound healing expression were then elucidated.</p><p><strong>Results: </strong>Our findings showed that both DSG and DSGO ointments significantly enhanced wound closure compared to the control groups. Histopathological and biochemical analyses indicated increased extracellular matrix production and fibroblasts, marked by improved fibroblast activity, neovascularization, and collagen deposition. Furthermore, immunohistochemistry and immunoblot analysis revealed that the ointments altered the expression of Ki67, α-smooth muscle actin (α-SMA), E-cadherin, vimentin, collagen, and components of the Smad signaling pathway, all of which are crucial for wound healing. The results also suggested that the DSGO ointment was marginally more effective in promoting wound healing in this model.</p><p><strong>Conclusions: </strong>These results indicate that ointment supplemented with DSG and DSGO have the potential to enhance skin repair by improving histopathology and altering wound healing-related proteins.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 11","pages":"388"},"PeriodicalIF":3.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-Infiltrating Lymphocytes in Triple-Negative Breast Cancer: Enduring Legacy, Emerging Evidence.","authors":"Wei Peng, Yayu Chen, Rong-Quan He, Gang Chen, Daniel Xin Zhang","doi":"10.31083/j.fbl2911385","DOIUrl":"https://doi.org/10.31083/j.fbl2911385","url":null,"abstract":"","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 11","pages":"385"},"PeriodicalIF":3.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The High Millimolar Concentration of ATP: A Fundamental & Foundational Feature of Eukaryotic, Archaeotic, and Prokaryotic Domains.","authors":"Jack V Greiner, Thomas Glonek","doi":"10.31083/j.fbl2911384","DOIUrl":"https://doi.org/10.31083/j.fbl2911384","url":null,"abstract":"<p><p>Measurement of the adenosine triphosphate (ATP) concentration among different cells, tissues and organs and even across the phylogenetic tree ordinarily yields exceedingly high concentrations at the millimolar (mM) level. This represents a conundrum in that ATP-driven cellular functions only require micromolar (μM) values. Considering that nature is ordinarily conservative in the generation of high-energy phosphatic metabolites such as ATP, a potential major role for ATP has been completely overlooked and may be of paramount importance because ATP is a hydrotrope. In all phylogenetic domains, reports have established that the excessively high mM concentration of ATP is present in studies of eukaryotic cellular and tissue homogenates, living tissues, and a living organ as well as archaeotic and prokaryotic organisms. These ATP concentrations are also present in contemporary relatives of microorganisms having progenitors existing in the Precambrian Era. This feature is fundamental to cell biology across taxonomic domains. These features are interpreted as serving a foundational molecular function for maintaining organismal homeostasis. We hypothesize that ATP prevents pathological protein aggregation and maintains protein solubility through its hydrotropic feature in cells, tissues, and organs.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 11","pages":"384"},"PeriodicalIF":3.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HMGB1 Modulates Macrophage Metabolism and Polarization in Ulcerative Colitis by Inhibiting Cpt1a Expression.","authors":"Fenfen Wang, Linfei Luo, Zhengqiang Wu, Lijun Wan, Fan Li, Zhili Wen","doi":"10.31083/j.fbl2911387","DOIUrl":"https://doi.org/10.31083/j.fbl2911387","url":null,"abstract":"<p><strong>Background: </strong>Macrophage polarization is involved in the development of ulcerative colitis (UC). This study investigated the mechanism by which high mobility group box-1 protein (HMGB1) regulates macrophage polarization through metabolic reprogramming, thereby contributing to the pathogenesis of UC.</p><p><strong>Methods: </strong>Dextran sulfate sodium (DSS) was used to induce colitis in mice. RAW264.7 cells were polarized to M1 or M2 macrophages <i>in vitro</i> by stimulating with lipopolysaccharide (LPS)/interferon-γ (IFN-γ) or Interleukin-4 (IL-4), respectively. Macrophage infiltration and distribution within colon tissue were assessed by immunohistochemistry and flow cytometry. Glycolysis, fatty acid oxidation (FAO), and inflammatory factors were evaluated using relevant reagent kits. Chromatin Immunoprecipitation (ChIP) and luciferase reporter experiments were performed to study the regulation of Carnitine palmitoyltransferase 1A (Cpt1a) promoter transcriptional activity by HMGB1.</p><p><strong>Results: </strong>The mouse UC model showed upregulated HMGB1 and increased macrophage infiltration. Overexpression of HMGB1 promoted M1 macrophage polarization, increased glycolysis, and reduced FAO, whereas knockdown of HMGB1 promoted M2 macrophage polarization, reduced glycolysis, and increased FAO. HMGB1 negatively regulated Cpt1a expression by inhibiting transcription of the Cpt1a promoter. Knockdown of Cpt1a reversed the effects of small interfering RNA targeting HMGB1 (si-HMGB1) on macrophage metabolism and polarization. Administration of adeno-associated virus (AAV)-shHMGB1 <i>in vivo</i> caused a reduction in UC symptoms and inflammation.</p><p><strong>Conclusions: </strong>HMGB1 modulates macrophage metabolism in UC by inhibiting Cpt1a expression, leading to increased M1 polarization. This provides a theoretical basis for the clinical application of HMGB1 inhibitors in the treatment of UC.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 11","pages":"387"},"PeriodicalIF":3.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Coenzyme Q₁₀ on Mitochondrial Metabolism: A Complementary Study Using Fluorescence Lifetime Imaging and Electron Microscopy.","authors":"Johannes Georg Wieland, Nilanjon Naskar, Kirsten Reess, Daniela Nobre Sarmento Dos Santos, Julia M Weise, Thomas Blatt, Sebastian Kordes, Paul Walther, Angelika Rück","doi":"10.31083/j.fbl2911383","DOIUrl":"https://doi.org/10.31083/j.fbl2911383","url":null,"abstract":"<p><strong>Background: </strong>Coenzyme Q₁₀ (CoQ₁₀), also known as ubiquinone-10, is an important molecule of the mitochondrial respiratory chain that acts as an electron carrier between complexes I, II, and III and additionally functions as an antioxidant. Due to its bioenergetic properties, CoQ₁₀ is of high interest for therapeutic and cosmetic use. This study aims to characterize the metabolic impact of CoQ₁₀ on primary human dermal fibroblasts (HDF) using fluorescence lifetime imaging microscopy (FLIM) and electron microscopy.</p><p><strong>Methods: </strong>FLIM of nicotinamide adenine dinucleotide (NADH) is a robust method to characterize cellular energy metabolism that also provides spatial information. Electron microscopy offers a way to characterize the ultrastructure of mitochondria and reveal features not visible in FLIM.</p><p><strong>Results: </strong>We reported a shift towards longer lifetimes of NADH in primary fibroblasts from ten different donors upon treatment with CoQ₁₀, which indicates the stimulation of oxidative phosphorylation. This is confirmed by phasor-based metabolic pattern segmentation, which showed localization of longer NADH lifetimes in CoQ₁₀-treated cells, indicating activated mitochondria in the cytoplasm. In addition, a complementary investigation of the mitochondrial ultrastructure using transmission electron microscopy (TEM) and scanning transmission electron microscopy (STEM) tomography showed a reduction in stress granules in CoQ₁₀-treated cells.</p><p><strong>Conclusions: </strong>Together, FLIM and electron microscopy (EM) imaging strongly imply that CoQ₁₀ stimulates cellular energy metabolism.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 11","pages":"383"},"PeriodicalIF":3.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boosted Meat Flavor by the Metabolomic Effects of Nile Tilapia Dietary Inclusion of <i>Zophobas atratus</i> Larval Meal.","authors":"Yanfeng Li, Haozheng Li, Ge Zhang, Jiale Liu, Dawa Drolma, Bo Ye, Manjun Yang","doi":"10.31083/j.fbl2911382","DOIUrl":"https://doi.org/10.31083/j.fbl2911382","url":null,"abstract":"<p><strong>Background: </strong><i>Zophobas atratus</i> larval meal (ZLM) is a high-quality feed supplement with potential activities that can improve fish growth performance and promote meat quality. However, there have been limited recent studies investigating the metabolic effects of ZLM. Therefore, this study aims to uncover the metabolomic mechanism through which ZLM improves tilapia meat flavor using metabolomic strategies.</p><p><strong>Method: </strong>In this study, soybean meal in the basal diets was replaced with 15%, 30%, or 60% ZLM, where anti-nutrient factors were destroyed by high temperature treatment. After being fed these ZLM supplements for 30 days, dorsal muscles were collected from tilapia for meat sensory evaluation tests. Liver samples were also collected for metabolomic analysis using the gas chromatography-mass spectrometry (GC-MS) platform and combined with biochemical assays to verify metabolism-related enzyme activities and reveal crucial metabolic pathways and critical biomarkers associated with ZLM's ability to improve meat flavor.</p><p><strong>Results: </strong>In tilapia livers, ZLM enhanced the activity of enzymes involved in energy metabolism including succinate dehydrogenase (SDH), pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase (α-KGDH), NADP-malate dehydrogenase (NAD-MDH) and mitochondrial isocitrate dehydrogenase (ICDHm). This resulted in increased levels of reduced nicotinamide adenine dinucleotide (NADH), acetyl CoA and ATP which led to accumulation of flavor fatty acids such as arachidonic acid, linoleic acid (9,12-Octadecadienoic acid), linolenic acid (9,12,15-Octadecatrienoic acid) and oleic acid (9-Octadecenoic acid). Additionally, there was an increase in flavor nucleotides like guanosine adenosine-5'-monophosphate and uridine-5'-monophosphate while off-flavor metabolites like inosine and hypoxanthine decreased. Furthermore, beneficial metabolomic responses led to a decrease in off-flavor metabolites such as 2-methylisoborneol trimethylamine and geosmin while increasing umami metabolites like 2-methyl-3-furanthiol and nonanal.</p><p><strong>Conclusions: </strong>This metabolomic study demonstrates that inclusion of ZLM diets enhances the flavor profile of tilapia dorsal muscle. The accumulation of flavor compounds, coupled with a reduction in earthy taste and off-flavor metabolites, contributes to an improved meat flavor and freshness. Additionally, there is an increase in the levels of flavor-related amino acids and nucleotides. These previously unidentified metabolic effects highlight the potential significance of ZLM as a dietary supplement for enhancing the biosynthesis of flavor metabolites in tilapia.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 11","pages":"382"},"PeriodicalIF":3.3,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium Iodate: Rapid and Clinically Relevant Model of AMD.","authors":"Jasmine S Geathers, Stephanie L Grillo, Ema Karakoleva, Gregory P Campbell, Yixuan Du, Han Chen, Alistair J Barber, Yuanjun Zhao, Jeffrey M Sundstrom","doi":"10.31083/j.fbl2911380","DOIUrl":"https://doi.org/10.31083/j.fbl2911380","url":null,"abstract":"<p><strong>Background: </strong>Age-related macular degeneration (AMD) is the most common cause of vision loss in people above the age of 50, affecting approximately 10% of the population worldwide and the incidence is rising. Hyperreflective foci (HRF) are a major predictor of AMD progression. The purpose of this study was to use the sodium iodate mouse model to study HRF formation in retinal degeneration.</p><p><strong>Methods: </strong>Sodium iodate (NaIO₃) treated rodents were studied to characterize HRF. 3-month-old male wild-type (WT) C57Bl/6J mice were injected with phosphate-buffered saline (PBS) or varying doses of NaIO₃ (15-60 mg/kg). Optical Coherence Tomography (OCT) images were collected at baseline and several days post-NaIO₃ injection. Retinal thicknesses were measured using Bioptigen software. Seven days post-injection, eyes were prepared for either transmission electron microscopy (TEM), Hematoxylin & Eosin (H&E), or immunofluorescence.</p><p><strong>Results: </strong>OCT imaging of the mice given higher doses of NaIO₃ revealed HRF formation in the neural retina (n = 4). The amount of HRF correlated with the degree of retinal tissue loss. H&E and TEM imaging of the retinas seven days post-NaIO₃ injection revealed several pigmented bodies in multiple layers of the retina (n = 3-5). Immunofluorescence revealed that some pigmented bodies were positive for macrophage markers and an epithelial-to-mesenchymal transition marker, while all were retinal pigment epithelium (RPE) 65-negative (n = 4).</p><p><strong>Conclusions: </strong>The data suggest that NaIO₃ induces the formation of HRF in the outer retina and their abundance correlates with retinal tissue loss. The experiments in this study highlight NaIO₃ as a clinically relevant model of intermediate AMD that can be used to study HRF formation and to discover new treatment targets.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"29 11","pages":"380"},"PeriodicalIF":3.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}