Investigative ophthalmology & visual science最新文献

{"title":"The TCF4 Gene Regulates Apoptosis of Corneal Endothelial Cells in Fuchs Endothelial Corneal Dystrophy.","authors":"Tatsuya Nakagawa, Tetsuro Honda, Taichi Yuasa, Go Nishiuchi, Masakazu Sato, Ayumi Tokunaga, Makiko Nakahara, Theofilos Tourtas, Ursula Schlötzer-Schrehardt, Friedrich Kruse, Prema Padmanabhan, Amit Chatterjee, Gajanan Sathe, Vivek Ghose, Narayanan Janakiraman, Derek J Blake, Noriko Koizumi, Sailaja Elchuri, Naoki Okumura","doi":"10.1167/iovs.66.3.16","DOIUrl":"10.1167/iovs.66.3.16","url":null,"abstract":"<p><strong>Purpose: </strong>Fuchs endothelial corneal dystrophy (FECD) is a progressive corneal disorder characterized by excessive extracellular matrix (ECM) accumulation and corneal endothelial cell death. CTG trinucleotide repeat expansion in the transcription factor 4 (TCF4) gene represents the most significant genetic risk factor. This study aimed to elucidate the role of TCF4 in FECD pathogenesis through comprehensive proteomic analysis.</p><p><strong>Methods: </strong>Corneal endothelial cells isolated from patients with FECD harboring TCF4 trinucleotide repeat expansion were immortalized to establish an FECD cell model (iFECD). CRISPR/Cas9-mediated genome editing was employed to generate TCF4-knockout iFECD cells. Whole-cell proteome analysis was performed using liquid chromatography-mass spectrometry, followed by pathway enrichment analysis of differentially expressed proteins (DEPs). The effects of TCF4 deletion on TGF-β-mediated protein aggregation and cell death were evaluated using Western blot analysis, flow cytometry, and aggresome detection assays.</p><p><strong>Results: </strong>Proteomic analysis identified 88 DEPs among 6510 detected proteins. Pathway analysis revealed significant enrichment in ECM-associated pathways, oxidative stress responses, and cellular motility. TCF4 deletion attenuated TGF-β-induced cell death in iFECD cells. Concordantly, Western blot analysis demonstrated that TCF4 deletion suppressed TGF-β2-mediated cleavage of caspase-3 and poly (ADP-ribose) polymerase. Flow cytometric analysis of Annexin V-positive cells confirmed reduced apoptosis in TCF4-deleted cells following TGF-β2 treatment. Additionally, aggresome detection assays revealed that TCF4 deletion diminished TGF-β2-induced protein aggregation.</p><p><strong>Conclusions: </strong>This study demonstrates a crucial role for TCF4 in FECD pathogenesis, particularly in ECM regulation and protein aggregation-induced cell death.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"16"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrosis-Related Gene and Protein Expression in Normal and Glaucomatous Trabecular Meshwork Cells.","authors":"Yong-Feng Yang, Paul Holden, Ying Ying Sun, Jennifer A Faralli, Donna M Peters, Kate E Keller","doi":"10.1167/iovs.66.3.48","DOIUrl":"10.1167/iovs.66.3.48","url":null,"abstract":"<p><strong>Purpose: </strong>Glaucomatous trabecular meshwork (GTM) tissue is characterized by excess fibrotic-like extracellular matrices, which negatively impacts aqueous humor outflow. Endothelial-to-mesenchymal transition (EndMT) is the process by which tissues develop fibrosis. In this study, we investigated fibrotic-related gene and protein profiles of non-glaucomatous trabecular meshwork (NTM) and GTM cells.</p><p><strong>Methods: </strong>Primary cells were cultured from NTM (n = 6) and GTM (n = 5) age-matched cadaver eyes. RNA was harvested and mRNA profiling of 750 genes was performed using the human fibrosis panel (NanoString). Quantitative PCR (qPCR), Western blotting, and immunofluorescence microscopy were performed. A matrix metalloproteinase (MMP) fluorogenic assay was used to quantitate enzyme activity.</p><p><strong>Results: </strong>Classic EndMT biomarkers, α-SMA, SNAI2, TWIST1, TWIST2, and VIM, were upregulated in GTM cells, whereas increased phosphorylated SMAD2-3 indicated increased TGFβ signaling. GTM cells had increased deposition of FN-EDA fibronectin fibrils, but reduced amounts of FN-EDB fibrils, and altered immunostaining of active α5β1 and αvβ3 integrins. NanoString analysis showed that 2 genes were upregulated and 28 genes were downregulated in GTM cells compared with NTM cells. Western immunoblotting confirmed increased protein levels of N-cadherin and decreased MMP2, CHI3L1, COL6A3, and SERPINF1 proteins in GTM cells. Whereas MMP2 gene and protein levels were reduced, there was increased MMP activity.</p><p><strong>Conclusions: </strong>Increased expression of α-SMA, FN-EDA, N-cadherin, SNAI2, TWISTs, VIM, TGFβ signaling, and MMP activity are consistent with GTM cells acquiring an EndMT phenotype. In combination with tissue studies, cultured GTM cells are a useful in vitro model for studying the fibrotic process in glaucoma.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"48"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide Association Study to Identify Genetic Variants Associated With Diabetic Maculopathy.","authors":"Rajya L Gurung, Charvi Nangia, Tengda Cai, Liesel M FitzGerald, Bennet J McComish, Ebony Liu, Georgia Kaidonis, Bronwyn Ridge, Alex W Hewitt, Brendan Vote, Nitin Verma, Jamie E Craig, Colin N A Palmer, Kathryn P Burdon, Weihua Meng","doi":"10.1167/iovs.66.3.55","DOIUrl":"10.1167/iovs.66.3.55","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic maculopathy (including diabetic macular edema [DME]) is the leading cause of vision loss in people with diabetes. We aimed to identify the genetic determinants of diabetic maculopathy.</p><p><strong>Methods: </strong>We conducted a genome-wide association study (GWAS) in two cohorts with a meta-analysis. The Australian cohort comprised 551 cases of DME and 599 controls recruited from the states of South Australia and Tasmania. The Scottish cohort comprised 1951 cases of diabetic maculopathy and 6541 controls from the Genetics of Diabetes Audit and Research in Tayside Scotland study (GoDARTS). Genotyping, imputation, and association analysis using logistic regression were conducted in each cohort, before combining summary statistics in a meta-analysis using the GWAMA package.</p><p><strong>Results: </strong>A locus on chromosome 7 reached genome-wide significance in GoDARTS but showed the opposite direction of effect in the Australian cohort. The meta-analysis identified two suggestive associations (P < 5 × 10-6) for diabetic maculopathy risk with similar effect direction; one at chromosome 1 close to the RNU5E-1 gene and one at chromosome 13 upstream of the ERICH6B gene. The two loci were evaluated in silico for potential functional links to diabetic maculopathy. Both are located in regulatory regions and have annotations indicating regulatory functions. They are also expression quantitative trait locus (eQTLs) for genes plausibly involved in diabetic maculopathy pathogenesis, with links to folate metabolism and the regulation of VEGF.</p><p><strong>Conclusions: </strong>The study suggests several promising SNPs and genes related to diabetic maculopathy risk. Despite being the largest genetic study of diabetic maculopathy to date, larger, homogeneous cohorts will be required to identify robust genetic risk loci for the disease.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"55"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diversity of Peripheral Refraction Patterns-Have These Been Oversimplified?","authors":"Megha Antony, Rakesh Maldoddi, David A Atchison, Pavan Kumar Verkicharla","doi":"10.1167/iovs.66.3.58","DOIUrl":"10.1167/iovs.66.3.58","url":null,"abstract":"<p><strong>Purpose: </strong>To describe patterns of peripheral refraction based on spherical equivalent refraction and on tangential and sagittal refractions, and to assess the association of peripheral refraction patterns with different central refractions.</p><p><strong>Methods: </strong>Peripheral refraction data from 737 individuals (14.7 ± 5.1 years old) were analyzed. Peripheral refraction was determined along the horizontal field at ±30° eccentricity using an open-field autorefractor in 89 hyperopes, 276 emmetropes, and 372 myopes. Values were converted into spherical equivalent refraction and into tangential and sagittal refractions. Nine different peripheral refraction patterns (A-I) were described based on spherical equivalent refraction, and 81 patterns were described based on tangential and sagittal refractions.</p><p><strong>Results: </strong>Using spherical equivalent refraction, all nine possible peripheral refraction patterns (A-I) were represented. Type I (relative peripheral myopia in nasal and temporal retinas) was seen in 40% of hyperopes, in 32% of emmetropes, and in 8% of myopes. Type A (relative peripheral hyperopia in nasal and temporal retinas) was seen in 20% of myopes and in ≤1% of hyperopes and emmetropes. No pattern was unique to any refractive group. Using tangential and sagittal refractions, 47 out of 81 possible patterns were represented. The three refractive groups shared 19 patterns in common. Hyperopes, emmetropes, and myopes had two, six, and eleven unique patterns, respectively.</p><p><strong>Conclusions: </strong>Many types of peripheral refraction patterns were observed, and these may provide insights into the complexities of eye growth and myopiogenesis. Tangential and sagittal refractions should be considered to understand peripheral refraction rather than spherical equivalent refraction alone.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"58"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11954539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Identification for Ocular Congenital Cranial Motor Neuron Disorders Using Human Sequencing, Zebrafish Screening, and Protein Binding Microarrays.","authors":"Julie A Jurgens, Paola M Matos Ruiz, Jessica King, Emma E Foster, Lindsay Berube, Wai-Man Chan, Brenda J Barry, Raehoon Jeong, Elisabeth Rothman, Mary C Whitman, Sarah MacKinnon, Cristina Rivera-Quiles, Brandon M Pratt, Teresa Easterbrooks, Fiona M Mensching, Silvio Alessandro Di Gioia, Lynn Pais, Eleina M England, Teresa de Berardinis, Adriano Magli, Feray Koc, Kazuhide Asakawa, Koichi Kawakami, Anne O'Donnell-Luria, David G Hunter, Caroline D Robson, Martha L Bulyk, Elizabeth C Engle","doi":"10.1167/iovs.66.3.62","DOIUrl":"10.1167/iovs.66.3.62","url":null,"abstract":"<p><strong>Purpose: </strong>To functionally evaluate novel human sequence-derived candidate genes and variants for unsolved ocular congenital cranial dysinnervation disorders (oCCDDs).</p><p><strong>Methods: </strong>Through exome and genome sequencing of a genetically unsolved human oCCDD cohort, we previously reported the identification of variants in many candidate genes. Here, we describe a parallel study that prioritized a subset of these genes (43 human genes, 57 zebrafish genes) using a G0 CRISPR/Cas9-based knockout assay in zebrafish and generated F2 germline mutants for 17. We tested the functionality of variants of uncertain significance in known and novel candidate transcription factor-encoding genes through protein binding microarrays.</p><p><strong>Results: </strong>We first demonstrated the feasibility of the G0 screen by targeting known oCCDD genes phox2a and mafba. Approximately 70% to 90% of gene-targeted G0 zebrafish embryos recapitulated germline homozygous null-equivalent phenotypes. Using this approach, we then identified three novel candidate oCCDD genes (SEMA3F, OLIG2, and FRMD4B) with putative contributions to human and zebrafish cranial motor development. In addition, protein binding microarrays demonstrated reduced or abolished DNA binding of human variants of uncertain significance in known and novel sequence-derived transcription factors PHOX2A (p.(Trp137Cys)), MAFB (p.(Glu223Lys)), and OLIG2 (p.(Arg156Leu)).</p><p><strong>Conclusions: </strong>This study nominates three strong novel candidate oCCDD genes (SEMA3F, OLIG2, and FRMD4B) and supports the functionality and putative pathogenicity of transcription factor candidate variants PHOX2A p.(Trp137Cys), MAFB p.(Glu223Lys), and OLIG2 p.(Arg156Leu). Our findings support that G0 loss-of-function screening in zebrafish can be coupled with human sequence analysis and protein binding microarrays to aid in prioritizing oCCDD candidate genes/variants.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"62"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956743/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pten Loss Triggers Progressive Photoreceptor Degeneration in an mTORC1-Independent Manner.","authors":"Joseph Hanna, Yacine Touahri, Alissa Pak, Luke Ajay David, Edwin van Oosten, Rajiv Dixit, Laura M Vecchio, Dhruv Nimesh Mehta, Ren Minamisono, Isabelle Aubert, Carol Schuurmans","doi":"10.1167/iovs.66.3.45","DOIUrl":"10.1167/iovs.66.3.45","url":null,"abstract":"<p><strong>Purpose: </strong>Silencing Phosphatase and tensin homolog (Pten) is a proposed therapeutic strategy for tissue regeneration to treat neurological disorders. However, Pten is pleiotropic, inhibiting several signaling and metabolic pathways, including mTORC1 and glycolysis, both pro-regenerative in certain contexts. This study aims to assess the long-term impact of inactivating Pten on photoreceptor survival in the retina and to identify downstream pathway(s).</p><p><strong>Methods: </strong>We assessed retinal integrity in Pten conditional knock-outs (cKOs) that were retinal progenitor cell (RPC)-specific (Pten RPC-cKO), a congenital model, or rod-specific (Pten Rho-cKO). We examined early changes in photoreceptor gene expression and used immunostaining to assess photoreceptors, reactive astrocytes, microglia, angiogenesis, and subretinal deposit formation from postnatal day (P) 21 to 1 year of age. Pten RPC-cKO retinal explants were treated with rapamycin, an mTOR inhibitor, or 2-deoxy-D-glucose (2DG), a glycolysis inhibitor.</p><p><strong>Results: </strong>In both Pten-cKO models, retinas display signs of early pathogenesis as photoreceptor-specific gene expression is downregulated at P0, before photoreceptor loss. Pten loss triggers progressive rod and cone degeneration beginning at P21 in Pten RPC-cKOs and at 6 months of age in Pten Rho-cKOs. Activated microglia and astrocytes, and increased angiogenesis, are observed in both Pten-cKO models, while subretinal amyloid-β deposits develop in Pten RPC-cKOs. Rapamycin accelerates photoreceptor degeneration in Pten RPC-cKOs, whereas 2DG has no effect.</p><p><strong>Conclusions: </strong>Our findings suggest that Pten loss, either in RPCs as a congenital model, or solely in mature rod photoreceptors, leads to progressive retinal degeneration that is exacerbated by mTORC1 suppression, drawing into question the therapeutic value of Pten-mTORC1 manipulations.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"45"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11935561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whorl-Like Collagen Fiber Arrangement Around Emissary Canals in the Posterior Sclera.","authors":"Hongshuang Lu, Yijin Wu, Jianping Xiong, Nan Zhou, Masahiro Yamanari, Michiaki Okamoto, Keigo Sugisawa, Hiroyuki Takahashi, Changyu Chen, Yining Wang, Ziye Wang, Kyoko Ohno-Matsui","doi":"10.1167/iovs.66.3.35","DOIUrl":"10.1167/iovs.66.3.35","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the collagen fiber arrangement around emissary canals in the posterior sclera.</p><p><strong>Methods: </strong>One hundred sixty-five eyes of 93 patients who underwent polarization-sensitive optical coherence tomography (PS-OCT) examinations in 2019 in the Institute of Science Tokyo were studied. Multimodal imaging, including streamline images derived from PS-OCT data, B-scan images, and indocyanine green angiography (ICGA) images, was used to investigate the collagen fiber arrangement around emissary canals and scleral pits in vivo. Additionally, the collagen fiber arrangement around the emissary canals in porcine sclera was examined using scanning electron microscopy and light microscopy.</p><p><strong>Results: </strong>Streamline images showed whorl-like collagen fiber arrangements on all eyes, and 25 eyes were selected for the analysis. All whorls corresponded to emissary canals on B-scan images. The whorls were confirmed to correspond to the posterior ciliary artery entries in three eyes and posterior vortex vein exits in three eyes with available ICGA images. Streamline cutaway images showed that the whorls surrounded the emissary canals throughout the entire course. In 16 eyes with 20 scleral pits, whorls were seen surrounding all the pits. Microscopic study using porcine sclera confirmed the whorl-like structures around the emissary canals ex vivo and demonstrated tangentially arranged collagen fiber bundles forming the circle.</p><p><strong>Conclusions: </strong>The collagen fibers are arranged as whorl-like structures around the vessel emissary canals in the posterior sclera, which is a knowledge gap for basic scleral histology. Additionally, this study demonstrated a strong correlation between PS-OCT findings and microscopic histology, underscoring PS-OCT's utility in detecting scleral collagen fiber arrangements.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"35"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corneal Keratocytes, Fibroblasts, and Myofibroblasts Exhibit Distinct Transcriptional Profiles In Vitro.","authors":"Kara Poole, Krithika S Iyer, David W Schmidtke, W Matthew Petroll, Victor D Varner","doi":"10.1167/iovs.66.3.28","DOIUrl":"10.1167/iovs.66.3.28","url":null,"abstract":"<p><strong>Purpose: </strong>After stromal injury to the cornea, the release of growth factors and pro-inflammatory cytokines promotes the activation of quiescent keratocytes into a migratory fibroblast and/or fibrotic myofibroblast phenotype. Persistence of the myofibroblast phenotype can lead to corneal fibrosis and scarring, which are leading causes of blindness worldwide. This study aims to establish comprehensive transcriptional profiles for cultured corneal keratocytes, fibroblasts, and myofibroblasts to gain insights into the mechanisms through which these phenotypic changes occur.</p><p><strong>Methods: </strong>Primary rabbit corneal keratocytes were cultured in either defined serum-free (SF) media, fetal bovine serum (FBS) containing media, or SF media supplemented with TGF-β1 to induce keratocyte, fibroblast, or myofibroblast phenotypes, respectively. Bulk RNA sequencing followed by bioinformatic analyses was performed to identify significant differentially expressed genes (DEGs) and enriched biological pathways for each phenotype.</p><p><strong>Results: </strong>Genes commonly associated with keratocytes, fibroblasts, or myofibroblasts showed high relative expression in SF, FBS, or TGF-β1 culture conditions, respectively. Differential expression and functional analyses revealed novel DEGs for each cell type, as well as enriched pathways indicative of differences in proliferation, apoptosis, extracellular matrix (ECM) synthesis, cell-ECM interactions, cytokine signaling, and cell mechanics.</p><p><strong>Conclusions: </strong>Overall, these data demonstrate distinct transcriptional differences among cultured corneal keratocytes, fibroblasts, and myofibroblasts. We have identified genes and signaling pathways that may play important roles in keratocyte differentiation, including many related to mechanotransduction and ECM biology. Our findings have revealed novel molecular markers for each cell type, as well as possible targets for modulating cell behavior and promoting physiological corneal wound healing.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"28"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11918030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143604805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a Hyperbaric Normoxic Environment on the Retina and Choroid.","authors":"Nur Demir, Belma Kayhan, Yavuz Aslan","doi":"10.1167/iovs.66.3.47","DOIUrl":"10.1167/iovs.66.3.47","url":null,"abstract":"<p><strong>Purpose: </strong>Divers and individuals working in submarines and other underwater environments are exposed to normoxic hyperbaric conditions frequently. The aim of this study was to evaluate the effects of hyperbaric normoxia on the retina and choroid.</p><p><strong>Methods: </strong>Healthy participants with no prior diving experience were exposed to 2.4 atmospheres absolute pressure in a normoxic hyperbaric chamber (HC). Optical coherence tomography was used to measure retinal thickness, the peripapillary retinal nerve fiber layer, and choroidal thickness (CT) before and within 30 minutes after HC exposure.</p><p><strong>Results: </strong>The right eyes of 42 participants (mean age, 23.88 ± 2.85 years) were included in the study. The retinal nerve fiber layer thickness significantly decreased in the central 1-mm Early Treatment Diabetic Retinopathy Study (ETDRS) subfield after HC exposure (P < 0.05). The outer plexiform layer showed significant thickening in the central 1-mm ETDRS subfield (P < 0.05). The retinal pigment epithelium (RPE) thickness in the 3-mm ETDRS subfield significantly decreased after HC exposure (P < 0.01). Furthermore, nasal CT (P < 0.05), temporal CT (P < 0.05), and mean CT (P < 0.01) significantly increased after HC exposure.</p><p><strong>Conclusions: </strong>This study is the first in which the effects of a hyperbaric normoxic environment on the retina and choroid were examined. The observed increases in outer plexiform layer and CTs may result from elevated intracranial perfusion pressure, likely owing to increased venous pressure with unchanged cerebral arterial blood flow under hyperbaric normoxic conditions. Elevated intracranial perfusion pressure may also contribute to venous stasis in the retinochoroidal circulation, potentially explaining the structural changes observed in this study.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"47"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11935558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Three-Dimensional β-Amyloid Burden Correlation Between the Eye and Brain in Alzheimer's Disease Mice Using Light-Sheet Fluorescence Microscopy.","authors":"Hye Joo Son, Seonok Kim, Seog-Young Kim, Jin Hwa Jung, Suk Hyun Lee, Soo-Jong Kim, Chanwoo Kim, Alice Hahn","doi":"10.1167/iovs.66.3.34","DOIUrl":"10.1167/iovs.66.3.34","url":null,"abstract":"<p><strong>Purpose: </strong>Recent studies have highlighted the significance of peripheral β-amyloid (Aβ) deposition, identifying the eye as a potential early detection site for Alzheimer's disease (AD). However, previous two-dimensional AD ocular studies have been unable to establish a clear correlation between the three-dimensional Aβ accumulation in the entire eyeball and brain while preserving structural integrity. This study employed a combined brain amyloid positron emission tomography/magnetic resonance (PET/MR) and light-sheet fluorescence microscopy (LSFM) platform to assess whether the three-dimensionally measured Aβ burden in the eyeball correlates with that in the brain.</p><p><strong>Methods: </strong>Thirteen eyeballs (6 AD, 7 control) and 17 brains (10 AD, 7 control) were collected from ten 44-week-old 5xFAD and seven control mice. The samples underwent tissue clearing and staining with thioflavin S (Aβ), anti-CD11b (microglia), and anti-ACSA-2 (astrocytes) for LSFM imaging and quantified via 3D surface volume. Standardized uptake value ratios from [18F]Flutemetamol PET/MR were also calculated.</p><p><strong>Results: </strong>AD eyeballs presented significantly greater plaque-like surface volumes (median, 51,091,002 µm³ [interquartile range, 38,488,272-64,869,828]) than controls (229,293 µm³ [115,863-311,5320]; P = 0.001). AD brains exhibited higher [18F]Flutemetamol uptake and greater plaque-like surface volumes (898,634,368 µm³ [556,263,488-1,105,326,720]) than controls (33,320,178 µm³ [26,842,538-62,716,956]; P < 0.001). A strong positive correlation was observed between the plaque-like surface volumes in the brain and that in the eyeball (r = 0.810, P = 0.001). No significant correlations were found in other morphologic parameters.</p><p><strong>Conclusions: </strong>Our observation of a strong correlation between the three-dimensional Aβ burden in the whole eyeball and brain advances our understanding of the systemic nature of Aβ pathology and suggests ocular Aβ as a potential independent predictor of brain Aβ burden.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"34"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143657069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}