Investigative ophthalmology & visual science最新文献

{"title":"RNA-Sequencing Reveals the Modulation of the NLRP3 Inflammasome by miR-223-3p in Extracellular Vesicles in Bacterial Endophthalmitis.","authors":"Dhanwini Rudraprasad, Jayabalan Nirmal, Dilip Kumar Mishra, Joveeta Joseph","doi":"10.1167/iovs.66.4.53","DOIUrl":"https://doi.org/10.1167/iovs.66.4.53","url":null,"abstract":"<p><strong>Purpose: </strong>Extracellular vesicles (EVs) are critical mediators of cell-cell communication via transfer of molecular cargo including miRNAs and regulate transcription in various physiological and pathological conditions. This study aimed to investigate the role of EV-derived-microRNAs (EV-miRNAs) in bacterial endophthalmitis, focusing on their regulatory impact on inflammation and host immune responses.</p><p><strong>Methods: </strong>C57BL/6 mice were infected with Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) to induce endophthalmitis. EVs were isolated and characterized followed by miRNA profiling to identify differentially expressed miRNAs. The miRNet platform was used to elucidate potential interactions between exosomal miRNA and retinal mRNA, followed by in vivo and in vitro validation of key miRNAs and their target genes. Additionally, EVs were extracted from vitreous fluid samples of patients with endophthalmitis, and miR-223-3p and NLRP3 expressions were assessed by qPCR.</p><p><strong>Results: </strong>Bacterial endophthalmitis led to pronounced neutrophil infiltration in the retina of mice. The miRNA profiling identified 651 differentially expressed miRNAs in P. aeruginosa and 29 in S. aureus, with 10 miRNAs shared between both infections. The miR-223-3p, miR-467a-3p, and miR-467d-3p emerged as major regulators of inflammatory pathways, targeting genes such as NLRP3, CXCL5, and IKKα. In patient vitreous samples, miR-223-3p was upregulated in culture-positive samples, correlating with reduced NLRP3 expression. The miRNAs, particularly miR-223-3p, play a critical role in modulating the immune response in bacterial endophthalmitis, largely through the regulation of the NLRP3 inflammasome.</p><p><strong>Conclusions: </strong>The findings suggest that miR-223-3p could serve as biomarkers in culture-negative cases and therapeutic targets for managing inflammation in bacterial endophthalmitis, potentially guiding treatments aimed at preserving retinal integrity.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"53"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005603","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":"Heterozygous Tcf4 Deficiency Mitigates Fuchs Endothelial Corneal Dystrophy Progression in a Mouse Model.","authors":"Suguru Ito, Yuki Oyama, Taichi Yuasa, Koki Amano, Kotaro Onishi, Ayaka Izumi, Albert S Jun, Masahito Ikawa, Noriko Koizumi, Naoki Okumura","doi":"10.1167/iovs.66.4.19","DOIUrl":"10.1167/iovs.66.4.19","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to use Col8a2Q455K/Q455K mice, an established Fuchs endothelial corneal dystrophy (FECD) model, to investigate whether heterozygous knockout of Tcf4 expression could ameliorate the progression of FECD.</p><p><strong>Methods: </strong>Tcf4 heterozygous knockout mice were generated using CRISPR/Cas9-mediated deletion of exons 2 and 3. These mice were crossed with Col8a2Q455K/Q455K mice to obtain Col8a2Q455K/Q455K/Tcf4± mice. Differential gene expression profiles in corneal endothelial cells of Col8a2Q455K/Q455K/Tcf4± and Col8a2Q455K/Q455K mice were then examined using RNA sequencing. Guttae formation and corneal endothelial cell density were assessed using contact specular microscopy. Expression of extracellular matrix (ECM) components was evaluated by qPCR and immunofluorescence analysis.</p><p><strong>Results: </strong>RNA-Seq analysis revealed 1053 differentially expressed genes between the Col8a2Q455K/Q455K/Tcf4± and the Col8a2Q455K/Q455K mice, with significant enrichment in ion channel-related pathways and downregulation of TNF-associated signaling pathways. Contact specular microscopy in 28-week-old mice demonstrated that guttae formation was significantly lower in the Col8a2Q455K/Q455K/Tcf4± mice than in the Col8a2Q455K/Q455K mice (0.71 ± 0.77% vs. 1.87 ± 1.43%, P < 0.001), whereas the corneal endothelial cell density was higher (1819 ± 170 vs. 1521 ± 292 cells/mm², P < 0.001). ECM components-particularly fibronectin and type I collagen, which are major constituents of guttae-were significantly decreased in the Col8a2Q455K/Q455K/Tcf4± mice.</p><p><strong>Conclusions: </strong>Heterozygous knockout of Tcf4 significantly suppressed the progression of the FECD phenotype, including guttae formation and endothelial cell loss, in the FECD mouse model. These findings provide in vivo support for TCF4 as a potential therapeutic target for FECD treatment.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"19"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984510/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803244","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":"Volumetric Measures of Capillary Nonperfusion on Optical Coherence Tomography Angiography Detect Early Ischemia in Diabetes Without Retinopathy.","authors":"Janice X Ong, Hunter J Lee, Nicole L Decker, Daniela Castellanos-Canales, Hisashi Fukuyama, Amani A Fawzi","doi":"10.1167/iovs.66.4.2","DOIUrl":"10.1167/iovs.66.4.2","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to compare volumetric 3-dimensional (3D) against standard 2-dimensional (2D) measurements of ischemia for distinguishing early stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA).</p><p><strong>Methods: </strong>This cross-sectional study considered 82 eyes of 82 patients (aged 51.0 ± 11.9 years) including 27 healthy controls, 31 patients with diabetes mellitus (DM) without DR, and 24 patients with mild nonproliferative DR (NPDR). Using OCTA, we obtained 2D scans and 3D volumes of the superficial capillary plexus (SCP), middle capillary plexus (MCP), and deep capillary plexus (DCP). We calculated geometric perfusion deficits (GPDs), which define ischemic regions as those located farther than a specified threshold distance from the nearest blood vessel. For the GPD parameter, we compared the performance of a 20 µm versus 30 µm cutoff.</p><p><strong>Results: </strong>On 2D scans, eyes with mild NPDR had significantly higher GPDs in all 3 retinal capillary layers, indicating worse ischemia, compared with both healthy controls and patients with DM without DR, using either threshold (20 µm or 30 µm) to define GPD (all P < 0.05). DM without DR showed no significant difference from healthy eyes in 2D images. Interestingly, however, using 3D volumes, DM without DR eyes had significantly greater DCP GPDs than healthy eyes using a GPD threshold of 20 µm (P = 0.012), but not with 30 µm (P = 0.057).</p><p><strong>Conclusions: </strong>Using a stringent threshold (20 µm), volumetric OCTA imaging detects significant DCP perfusion defects in diabetic eyes even before DR onset, whereas traditional 2D OCTA does not. Volumetric scans may therefore be more sensitive to early ischemia in diabetes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"2"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763420","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":"Progression of Atrophy as a Function of ABCA4 Variants and Age of Onset in Stargardt Disease.","authors":"Jeroen A A H Pas, Catherina H Z Li, Filip Van den Broeck, Patty P A Dhooge, Julie De Zaeytijd, Rob W J Collin, Bart P Leroy, Carel B Hoyng","doi":"10.1167/iovs.66.4.76","DOIUrl":"https://doi.org/10.1167/iovs.66.4.76","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to assess the natural course of the retinal atrophy growth rate in patients with Stargardt disease (STGD1) with particular mutations in ABCA4, which may be eligible for mutation-specific therapy.</p><p><strong>Methods: </strong>Fundus autofluorescence images (Heidelberg Spectralis) were gathered from 221 patients (436 eyes) in two centers: Radboud UMC and Ghent University Hospital. The area of definitely decreased autofluorescence and total decreased autofluorescence was measured using the Heidelberg RegionFinder software tool. Square root transformation was used to correct for two-dimensional growth. A mixed model was used to determine the atrophy growth rates. Atrophy growth rates were calculated for all eyes and were categorized into subgroups based on ABCA4 mutations potentially suitable for mutation-specific therapy (c.4539+2001G>A; c.5461-10T>C; c.5882G>A; c.768G>T), or subgroups based on age of onset.</p><p><strong>Results: </strong>The mean square root-transformed growth rate of atrophy was 0.1446 mm/year (95% CI, 0.1382-0.1510 mm/year) for definitely decreased autofluorescence and 0.1459 mm/year (95% CI, 0.1402-0.1515 mm/year) for total decreased autofluorescence. Definitely decreased autofluorescence square root-transformed atrophy growth was slower in patients heterozygous for c.5882G>A (0.0821 mm/year) and c.4539+2001G>A (0.0686 mm/year) than c.768G>T (0.1299 mm/year) and c.5461-10T>C (0.1565 mm/year). Eyes of patients with late-onset STGD1 had the fastest atrophy growth (0.1782 mm/year), compared with eyes of patients with early-onset STGD1 (0.1655 mm/year) and patients with intermediate-onset STGD1 (0.1269 mm/year).</p><p><strong>Conclusions: </strong>Atrophy growth rates vary among subgroups of patients with STGD1, depending on both specific mutations and age of onset. This pattern may have implications for the design of clinical trials for mutation-specific therapies.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"76"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971712","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":"Quantitative Stain-Free Conjunctival Collagen Imaging in Cicatrizing Conjunctivitis Using Second Harmonic Generation-Two Photon Excitation Technology.","authors":"Ralene Sim, Andri K Riau, Nuur Shahinda Humaira Binte Halim, Jodhbir S Mehta, Hon Shing Ong","doi":"10.1167/iovs.66.4.49","DOIUrl":"https://doi.org/10.1167/iovs.66.4.49","url":null,"abstract":"<p><strong>Purpose: </strong>We aim to study the structure of collagen in cicatrizing conjunctivitis (CC), a disease with significant morbidity, to find sensitive and quantitative measures of severity of scarring as current progression of conjunctival scarring is reliant only on clinical assessment.</p><p><strong>Methods: </strong>We used two-photon excitation and second harmonic generation to scan conjunctival tissues from patients with CC from Stevens-Johnson syndrome and its relation to disease severity by correlation with a validated clinical severity assessment tool. Collagen morphometry in region of interest was analyzed with FibroIndex software (HistoIndex Pte Ltd.) in conjunctival biopsies.</p><p><strong>Results: </strong>Eighteen patients (seven CC and 11 controls) were included. Mean age was 60.7 ± 14.4 years old, with no difference between groups (P = 0.89) Compared to controls, diseased group has significantly smaller collagen area ratio (CAR) (P < 0.01), collagen fiber number (CFN)/mm2 (P < 0.01) and larger collagen fiber density (P = 0.03) In diseased groups, CAR correlated with inflammation (R = -0.55, P = 0.011), scarring (R = 0.61, P = 0.0034), morbidity (R = 0.46, P = 0.035) and overall composite score (R = 0.52, P = 0.017). In all groups, CFN/mm2 negatively correlated with inflammation (R = -0.50, P < 0.01), scarring (R = -0.25, P = 0.07) morbidity (R = -0.37, P < 0.01), and overall composite score (R = -0.33, P = 0.02).</p><p><strong>Conclusions: </strong>We have further characterized the defining features in CC. CAR has significant correlation to all scores in diseased groups and, hence, may be a reliable marker for diagnosis. CFN/mm2, as the only parameter with significant negative correlation with all scores, can potentially be a predictor for severity.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"49"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024326","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":"Radiomics Analysis Based on Optical Coherence Tomography to Prognose the Efficacy of Anti-VEGF Therapy of Retinal Vein Occlusion-Related Macular Edema.","authors":"Biying Chen, Jianing Qiu, Yongan Meng, Youling Liang, Dan Liu, Yuqian Hu, Zhishang Meng, Jing Luo","doi":"10.1167/iovs.66.4.74","DOIUrl":"https://doi.org/10.1167/iovs.66.4.74","url":null,"abstract":"<p><strong>Purpose: </strong>Anti-vascular endothelial growth factor (anti-VEGF) agents are the first-line treatment for retinal vein occlusion-related macular edema (RVO-ME). However, the availability of reliable radiomic markers for evaluating the effectiveness of these agents is currently limited. The aim of this study was to develop machine learning approaches to evaluate the post-therapeutic effect of anti-VEGF treatment based on optical coherence tomography (OCT) images.</p><p><strong>Methods: </strong>A total of 152 patients diagnosed with RVO-ME who received at least one intravitreal injection of anti-VEGF were included in this study, as well as 81 patients as the external validation set. Pre-therapeutic B-scans of spectral-domain OCT images were collected and segmented using the Pyradiomics module within the 3D Slicer software platform. Radiomic features were extracted from the segmented images. We trained the logistic regression model and machine learning models using the selected features, and evaluated the performance of the three classifier models.</p><p><strong>Results: </strong>In the back propagation neural network (BPNN) model, the area under the curve (AUC) of the training, test, and external validation sets were 0.977, 0.912, and 0.804, respectively. In the support vector machine (SVM) model, the AUC of the 3 sets were 0.916, 0.882, and 0.802. The OCT-omics scores indicated a high overall net benefit, as determined by decision curve analysis.</p><p><strong>Conclusions: </strong>The machine learning models based on OCT technology developed here demonstrated a promising ability to prognose anti-VEGF therapeutic responses for RVO-ME. The utilization of machine learning provides a new promising approach to assessing radiomic markers in research related to RVO-ME, having a good prospect for the application of the using of precision medicine in ophthalmology.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"74"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025012","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":"A Novel AAV Capsid-Mediated RS1 Gene Therapy Restored Retinal Function to Wild-Type Levels in Rs1R213W Mouse Model.","authors":"Xing Wei, Sisi Ma, Yunyu Zhou, Haoliang Cui, Shan Zhang, Duanyang Wang, Yingying Fu, Wei Li, Huihui Han, Yamei Li, Wuyi Li, Huixin Liu, Zixi Sun, Xiaoxu Han, Xuan Zou, Hui Li, Cheng Wang, Ruifang Sui","doi":"10.1167/iovs.66.4.37","DOIUrl":"https://doi.org/10.1167/iovs.66.4.37","url":null,"abstract":"<p><strong>Purpose: </strong>X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by retinoschisin 1 (RS1) gene variants, potentially leading to severe visual impairment and blindness. This study aimed to develop a novel adeno-associated virus (AAV) serotype and evaluate its therapeutic potential in an XLRS mouse model.</p><p><strong>Methods: </strong>A novel RS1 mouse model was established using the CRISPR-Cas9 gene editing system and underwent phenotypic characterization. AAV.IVT18-scRS/CMV-RS1, comprising a rationally designed novel capsid (AAV.IVT18) and an optimized RS1 gene expression cassette, was then constructed and delivered via intravitreal injection into mutant and wild-type (WT) mice at 3 to 4 weeks of age. Retinal structure, function, and inflammation levels were evaluated after treatment.</p><p><strong>Results: </strong>A novel mouse model harboring the patient-derived RS1 missense variant R213W was generated, accurately recapitulating the human phenotype. We developed a novel AAV serotype, AAV.IVT18, which efficiently transfected photoreceptor and bipolar cells by intravitreal injection, and optimized the expression cassettes of RS1. AAV.IVT18-mediated expression of RS1 ameliorated retinoschisis in the mouse model and normalized the b/a ratio of the mouse electroretinogram (ERG). Remarkably, the ERG b-wave amplitudes of the treated groups began to increase at 8 weeks post-injection and recovered to the WT mouse level by 16 weeks of injection. Inflammatory activation in Rs1R213W mice was alleviated by treatment.</p><p><strong>Conclusions: </strong>The novel AAV capsid-mediated RS1 gene therapy effectively improved retinal structure and function while downregulating inflammation in Rs1R213W mice. These results provide a robust foundation for future clinical trials on XLRS gene therapy, offering the potential to improve the vision and quality of life of patients.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"37"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996675","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":"Fluorescence Lifetime Imaging Ophthalmoscopy, Vision, and Chorioretinal Asymmetries in Aging and Age-Related Macular Degeneration: ALSTAR2.","authors":"Lukas Goerdt, Mark E Clark, Tracy N Thomas, Liyan Gao, Gerald McGwin, Martin Hammer, Jason N Crosson, Kenneth R Sloan, Cynthia Owsley, Christine A Curcio","doi":"10.1167/iovs.66.4.56","DOIUrl":"https://doi.org/10.1167/iovs.66.4.56","url":null,"abstract":"<p><strong>Purpose: </strong>Eyes with age-related macular degeneration (AMD) and some healthy aged eyes exhibit risk-indicating delays in rod-mediated dark adaptation (RMDA) and prolonged long spectral channel (LSC) lifetimes by fluorescence lifetime imaging ophthalmoscopy (FLIO) in the Early Treatment Diabetic Retinopathy Study (ETDRS) outer ring, especially nasally. To learn FLIO's potential for AMD detection, we correlate FLIO to RMDA.</p><p><strong>Methods: </strong>The ALSTAR2 follow-up cohort underwent FLIO, color fundus photography, two-wavelength autofluorescence (for macular pigment optical density [MPOD]), visual function testing, including RMDA (rod intercept time [RIT]). AMD was staged by the Age-Related Eye Disease Study (AREDS) 9-step at baseline and follow-up. In pseudophakic eyes with high-quality FLIO, mean intensity maps and meridian plots were created. Vision data were analyzed using linear regression and Spearman's r.</p><p><strong>Results: </strong>Of 155 eyes (155 participants [75 ± 5.0 years; 60.7% female participants]), 67 eyes were healthy, 38 had early (e)AMD, and 50 had intermediate (i)AMD (P = 0.02). LSC lifetimes were longest in iAMD in all ETDRS regions (P < 0.01) and short spectral channel (SSC) lifetimes in inner and outer rings (P < 0.01). The LSC pattern manifested in 65 of 88 AMD eyes and 30 of 67 healthy eyes. Lifetimes were longest on the nasal meridian and shortest on temporal. LSC lifetimes in the inner and outer rings correlated strongly with RIT (r = 0.68). A stable subgroup had short LSC lifetimes and short RIT. SSC correlated weakly with MPOD.</p><p><strong>Conclusions: </strong>Prolonged lifetimes in AMD exhibit spatial asymmetry, suggesting mechanisms beyond retinal cells and including choroid. Lifetimes correlate with delayed RMDA, potentially indicating risk for AMD onset and early progression. Further research into SSC signal sources is warranted.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"56"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991474","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":"Temporal Frequency Modulation of Binocular Balance in Normal and Amblyopic Vision.","authors":"Chenyan Zhou, Jiawei Zhou, Seung Hyun Min","doi":"10.1167/iovs.66.4.8","DOIUrl":"10.1167/iovs.66.4.8","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate how temporal frequency modulates binocular balance in normally sighted and amblyopic adults.</p><p><strong>Methods: </strong>Twenty-three controls and 13 amblyopes participated in this study. The effects of temporal frequency differences and monocularly directed attention on binocular balance were measured using an onset binocular rivalry task with sinusoidally flickering gratings at varying temporal frequencies and static gratings with monocular attentional cues. For the flickering gratings, different combinations of temporal frequencies (2, 4, or 10 Hz in one eye vs. 2, 3, 4, 6, 10, 15, or 20 Hz in the other) were presented. Their effects were then compared, and their relationship was analyzed.</p><p><strong>Results: </strong>There was no relationship between the shifts in balance from temporal frequency and monocularly directed attention in both controls and amblyopes. Intermediate temporal frequencies (8.9 ± 1.4 Hz) in one eye maximized its perceptual dominance, with a larger shift due to temporal frequency in amblyopes than in controls. While normally sighted observers experienced similar degrees of shift in balance from temporal frequency and attentional (active and passive) modulations, amblyopic observers experienced a larger shift from temporal frequency than from monocularly focused passive (but not active) attention.</p><p><strong>Conclusions: </strong>Intermediate temporal frequencies in one eye, rather than a specific temporal frequency difference between both eyes, maximized its perceptual dominance in both normally sighted and amblyopic observers. This balance shift from temporal frequency modulation was larger in amblyopes than in controls. Finally, the effect of temporal frequency on balance was larger than that of monocularly directed passive attention in amblyopes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"8"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11967993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763387","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 Verteporfin on Interstitial Fluid Flow-Induced Fibrotic Transdifferentiation of Human Tenon Fibroblasts.","authors":"Janne Frömmichen, Emma Bungert, Jeanne Ströble, Moritz Gläser, Charlotte Gottwald, Kosovare Zeqiri, Thomas Reinhard, Jan Lübke, Günther Schlunck, Cornelius Jakob Wiedenmann","doi":"10.1167/iovs.66.4.17","DOIUrl":"10.1167/iovs.66.4.17","url":null,"abstract":"<p><strong>Purpose: </strong>Postoperative scarring remains the major challenge in achieving long-term success after glaucoma filtration surgery. In a previous study, we showed that slow continuous fluid flow is sufficient to induce fibrotic responses in human tenon fibroblasts (HTFs) in two-dimensional (2D) and three-dimensional (3D) in vitro models. In the present study, we investigated the role of the mechanosensitive Yes-associated protein (YAP) and transcriptional coactivator (TAZ) signaling pathway in flow-induced fibrosis.</p><p><strong>Methods: </strong>HTFs were exposed to continuous fluid flow for 48 or 72 hours in the presence or absence of the YAP/TAZ-transcriptional enhanced associated domain inhibitor verteporfin (VP). In a 2D model, the F-actin cytoskeleton, fibronectin 1 (FN1), YAP, and TAZ were visualized by confocal immunofluorescence microscopy. In a 3D model, mRNA was extracted, and the expression of fibrosis-associated genes was detected by quantitative PCR.</p><p><strong>Results: </strong>HTFs exposed to slow fluid flow showed increased staining intensities for YAP/TAZ. Inhibition of YAP/TAZ by VP slightly reduced flow-induced fibrotic changes in the 2D model. The flow-induced increase in the expression of the extracellular matrix (ECM) genes COL1A1, CTGF, and FN1 was significantly inhibited by VP in the 3D model.</p><p><strong>Conclusions: </strong>Slow interstitial fluid flow activates the YAP/TAZ pathway. VP exerts antifibrotic potential by reducing morphologic changes and suppressing the expression of ECM genes induced by flow. Therefore, YAP/TAZ inhibition may exhibit therapeutic potential after glaucoma filtration surgery by inhibiting fibrotic changes induced by mechanical stimuli.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"17"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11993124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803317","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}