Investigative ophthalmology & visual science最新文献

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Longitudinal Imaging of the Foveal Cone Mosaic in CNGA3-Associated Achromatopsia. CNGA3相关性色弱眼眼窝锥体镶嵌的纵向成像
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.6
Mohamed Katta, Michalis Georgiou, Navjit Singh, Angelos Kalitzeos, Alfredo Dubra, Joseph Carroll, Michel Michaelides
{"title":"Longitudinal Imaging of the Foveal Cone Mosaic in CNGA3-Associated Achromatopsia.","authors":"Mohamed Katta, Michalis Georgiou, Navjit Singh, Angelos Kalitzeos, Alfredo Dubra, Joseph Carroll, Michel Michaelides","doi":"10.1167/iovs.65.12.6","DOIUrl":"10.1167/iovs.65.12.6","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to assess the natural history of the foveal cone mosaic in CNGA3-associated achromatopsia (ACHM).</p><p><strong>Methods: </strong>Thirteen eyes from 10 genetically confirmed patients underwent longitudinal imaging with optical coherence tomography (OCT) and non-confocal split detection adaptive optics scanning light ophthalmoscopy (AOSLO). OCT scans assessed outer nuclear layer (ONL) thickness, foveal ellipsoid zone (EZ) disruption, and foveal hypoplasia. AOSLO images were analyzed to calculate peak foveal cone density (PCD) and mean inter-cell distance (ICD) between cones. Mixed effects models were used to analyze the rate of annual change of PCD and ICD.</p><p><strong>Results: </strong>Mean (±SD) age at visits was 29 ± 10 years, with a follow-up of 2.6 ± 1 years. There was no change in ONL thickness, degree of EZ disruption, or foveal hypoplasia over the follow-up period. We also observed a stable foveal cone mosaic using AOSLO imaging, with no significant change in PCD or ICD. Mean PCD was 15,346 cones/mm² at the mean age of 29 years old (cf. 64,000-324,000 cones/mm² in previously reported healthy controls), with a mean rate of change of -117.79 cones/mm² (0.8%) per year, P = 0.130. Mean ICD at the mean age was 13.82 µm, with a rate of change of 0.17 µm per year, P = 0.83.</p><p><strong>Conclusions: </strong>CNGA3-associated ACHM displays stable foveal cone structure over time with a similar rate of change to CNGB3-associated ACHM (2% decline per year). The stable PCD, small cohort, and large variability within the cohort means significant age associations were not detected.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371858","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}
引用次数: 0
Association of Ambient Air Pollution Exposure With Incident Glaucoma: 12-Year Evidence From the UK Biobank Cohort. 环境空气污染暴露与青光眼发病率的关系:英国生物库队列 12 年的证据。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.22
Zihan Sun, Kelsey V Stuart, Robert N Luben, Amy L Auld, Nicholas G Strouthidis, Peng T Khaw, Hari Jayaram, Anthony P Khawaja, Paul J Foster
{"title":"Association of Ambient Air Pollution Exposure With Incident Glaucoma: 12-Year Evidence From the UK Biobank Cohort.","authors":"Zihan Sun, Kelsey V Stuart, Robert N Luben, Amy L Auld, Nicholas G Strouthidis, Peng T Khaw, Hari Jayaram, Anthony P Khawaja, Paul J Foster","doi":"10.1167/iovs.65.12.22","DOIUrl":"https://doi.org/10.1167/iovs.65.12.22","url":null,"abstract":"<p><strong>Purpose: </strong>Glaucoma is the leading cause of irreversible blindness worldwide. Despite growing concerns about air quality and its impact on ocular health, there remains a knowledge gap regarding the long-term association between air pollution and glaucoma risk. This study investigates the relationship between exposure to ambient air pollution and incidence of glaucoma.</p><p><strong>Methods: </strong>In this prospective study, we used land use regression models to estimate levels of various air pollutants, including fine particulate matter (PM2.5), PM2.5 absorbance, PM2.5-10, PM10, nitrogen dioxide (NO2), and nitrogen oxides (NOx). Incidents of glaucoma were ascertained through routinely collected hospital admission records. Multivariate Cox proportional hazards models were used to examine the associations between air pollution exposure and glaucoma incidence, adjusting for potential confounding sociodemographic, physical, and lifestyle factors.</p><p><strong>Results: </strong>Data from 481,113 participants were included. Over a median follow-up of 12.8 years, 9224 incident cases of glaucoma were identified. In the maximally adjusted model, per interquartile range increase in PM2.5 was associated with a 3% greater risk of developing glaucoma (hazard ratio [HR] = 1.03, 95% confidence interval [CI] = 1.00 to 1.06, P = 0.048). Participants in the highest quartile had a 10% increased risk of developing glaucoma compared to those in the lowest quartile (HR = 1.10, 95% CI = 1.03 to 1.17, P = 0.005).</p><p><strong>Conclusions: </strong>Higher levels of exposure to ambient air pollutants, particularly PM2.5, are associated with an increased risk of developing glaucoma. These results highlight the potential public health impact of ambient air pollution on glaucoma risk and underscore the urgent need for further research into targeted environmental interventions in this domain.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465679","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}
引用次数: 0
ALKBH5 Regulates Corneal Neovascularization by Mediating FOXM1 M6A Demethylation. ALKBH5 通过介导 FOXM1 M6A 去甲基化调控角膜新生血管形成
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.34
Wei Wang, Hua Li, Yiyong Qian, Min Li, Manli Deng, Dexi Bi, Jun Zou
{"title":"ALKBH5 Regulates Corneal Neovascularization by Mediating FOXM1 M6A Demethylation.","authors":"Wei Wang, Hua Li, Yiyong Qian, Min Li, Manli Deng, Dexi Bi, Jun Zou","doi":"10.1167/iovs.65.12.34","DOIUrl":"10.1167/iovs.65.12.34","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to explore the regulatory role and potential mechanisms of ALKBH5-mediated N6-methyladenosine (m6A) demethylation modification in corneal neovascularization (CNV).</p><p><strong>Methods: </strong>A mouse CNV model was established through corneal alkali burns. Total m6A levels were measured using an m6A RNA methylation quantification kit. The mRNA expression of candidate m6A-related enzymes was quantified by quantitative RT-PCR. Small interfering RNA targeting ALKBH5 was injected subconjunctivally into alkali-burned mice. The CNV area, corneal epithelial thickness, and pathological changes were evaluated. Protein expression was detected by western blot and immunofluorescence. Human umbilical vein endothelial cells (HUVECs) were treated with IL-6. Plasmid transfection knocked down ALKBH5 or overexpressed FOXM1 in IL-6-induced HUVECs. The assays of CCK8, wound healing, and tube formation evaluated the cell proliferation, migration, and tube formation abilities, respectively. The dual-luciferase assay examined the binding between ALKBH5 and FOXM1. Methylated RNA immunoprecipitation-qPCR detected the m6A levels of FOXM1.</p><p><strong>Results: </strong>Significant CNV was observed on the seventh day. Total m6A levels were reduced, and ALKBH5 expression was increased in CNV corneas and IL-6-induced HUVECs. ALKBH5 knockdown alleviated corneal neovascularization and inflammation and countered IL-6-induced promotion of cell proliferation, migration, and tube formation in HUVECs. ALKBH5 depletion increased m6A levels and decreased VEGFA and CD31 expression both in vivo and in vitro. This knockdown in HUVECs elevated m6A levels on FOXM1 mRNA while reducing its mRNA and protein expression. Notably, FOXM1 overexpression can reverse ALKBH5 depletion effects.</p><p><strong>Conclusions: </strong>ALKBH5 modulates FOXM1 m6A demethylation, influencing CNV progression and highlighting its potential as a therapeutic target.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500604","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}
引用次数: 0
Differential Localization and Functional Roles of mGluR6 Paralogs in Zebrafish Retina. 斑马鱼视网膜中 mGluR6 Paralogs 的不同定位和功能作用
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.44
Marion Haug, Sara A Haddad-Velioglu, Manuela Berger, Anja Enz, Jingjing Zang, Stephan C F Neuhauss
{"title":"Differential Localization and Functional Roles of mGluR6 Paralogs in Zebrafish Retina.","authors":"Marion Haug, Sara A Haddad-Velioglu, Manuela Berger, Anja Enz, Jingjing Zang, Stephan C F Neuhauss","doi":"10.1167/iovs.65.12.44","DOIUrl":"https://doi.org/10.1167/iovs.65.12.44","url":null,"abstract":"<p><strong>Purpose: </strong>To define the location of mglur6 paralogs in the outer zebrafish retina and delineate their contribution to retina light responses across the visual spectrum.</p><p><strong>Methods: </strong>In situ hybridization and immunolocalization with custom-made antibodies were used to localize mglur6 transcripts, proteins, and additional components of the mGluR6 signaling complex. Gene editing was used to generate knockout mutants that were analyzed with white light and spectral electroretinography.</p><p><strong>Results: </strong>Both mglur6 paralogs colocalized with known downstream pathway genes, such as trpm1a, nyctalopin, and gnaoβ. All rod photoreceptors contacted mGluR6-positive cells, while cone connectivity presented a more complex situation with no red cones and only a few UV and blue-sensitive cones connecting to mGluR6a-positive bipolar cells. All cone subtypes contacted mGluR6b-positive cells with markedly fewer red-sensitive cones. Retinas of knockout animals displayed no morphologic alterations. While ERG responses were unaffected in mglur6a knockout animals, mglur6b mutants displayed decreased responses over all spectral wavelengths.</p><p><strong>Conclusions: </strong>We demonstrated that mGlurR6 signalplex components are similar in the zebrafish and the mammalian retina. Despite mglur6b knockout animals having significantly impaired ERG b-wave responses, a residual b-wave persists, even in double knockouts, suggesting additional pathway components yet to be identified.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optimizing Subretinal Bleb Formation for Visual Streak Involvement in a Porcine Model for Retinal Gene Therapy. 在猪视网膜基因治疗模型中优化视网膜下出血点的形成,以实现视觉条纹参与。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.41
Immanuel P Seitz, Tobias Peters, Felix Reichel, Andrea Bähr, Hanna Auch, Jan Motlik, Taras Ardan, Jana Juhasova, Yaroslav Nemesh, Stefan Juhás, Nikolai Klymiuk, Manuel Dominik Fischer
{"title":"Optimizing Subretinal Bleb Formation for Visual Streak Involvement in a Porcine Model for Retinal Gene Therapy.","authors":"Immanuel P Seitz, Tobias Peters, Felix Reichel, Andrea Bähr, Hanna Auch, Jan Motlik, Taras Ardan, Jana Juhasova, Yaroslav Nemesh, Stefan Juhás, Nikolai Klymiuk, Manuel Dominik Fischer","doi":"10.1167/iovs.65.12.41","DOIUrl":"10.1167/iovs.65.12.41","url":null,"abstract":"<p><strong>Purpose: </strong>Subretinal (SR) injection in porcine models is a promising avenue for preclinical evaluation of cell and gene therapies. Targeting of the subretinal fluid compartment (bleb) is critical to the procedure, especially if treatment of the cone-rich area centralis is required (i.e., visual streak [VS] in pigs). To our knowledge, this study is the first to investigate the influence of injection site placement on VS involvement in the pig eye.</p><p><strong>Methods: </strong>We performed 23-gauge pars plana vitrectomy followed by SR injection in 41 eyes of 21 animals (Sus scrofa domesticus). In 27 eyes (65.9%), the injection site was placed superior to the VS, and in 14 eyes (34.1%) it was placed inferior to it. Using intraoperative imaging, blebs were classified based on their propagation behavior relative to the VS.</p><p><strong>Results: </strong>In 79% of cases, blebs from inferior injection sites developed away from the VS, exhibiting a mean ± SEM vertical anisotropy (AP) of 0.67 ± 0.11. In contrast, blebs from superior injection sites tended to develop toward the VS with an AP of 1.27 ± 0.18 (P = 0.0070). Blebs developed away from the VS in only 41% of injections (P = 0.0212). Inferior blebs were orientated close to 0° (horizontal), whereas superior blebs displayed varied orientations with a mean angle of 56° (P = 0.0008).</p><p><strong>Conclusions: </strong>Bleb propagation was anisotropic (i.e., directionally biased) and dependent on injection site placement. Superior injection sites led to superior VS detachment. Morphological analysis suggested increased adhesion forces at the VS and superior vascular arcades. This study will aid the planning of surgeries for targeted subretinal delivery in pig models.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500608","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}
引用次数: 0
Initial Retinal Nerve Fiber Layer Loss and Risk of Diabetic Retinopathy Over a Four-Year Period. 最初视网膜神经纤维层缺损与四年内糖尿病视网膜病变的风险
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.5
Xiaoying Zhong, Huangdong Li, Shaoying Tan, Shaopeng Yang, Ziyu Zhu, Wenyong Huang, Weijing Cheng, Wei Wang
{"title":"Initial Retinal Nerve Fiber Layer Loss and Risk of Diabetic Retinopathy Over a Four-Year Period.","authors":"Xiaoying Zhong, Huangdong Li, Shaoying Tan, Shaopeng Yang, Ziyu Zhu, Wenyong Huang, Weijing Cheng, Wei Wang","doi":"10.1167/iovs.65.12.5","DOIUrl":"10.1167/iovs.65.12.5","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate whether the rapid rate of peripapillary retinal nerve fiber layer (pRNFL) thinning in short-term is associated with the future risk of developing diabetic retinopathy (DR).</p><p><strong>Methods: </strong>This prospective cohort study utilized 4-year follow-up data from the Guangzhou Diabetic Eye Study. The pRNFL thickness was measured by optical coherence tomography (OCT). DR was graded by seven-field fundus photography after dilation of the pupil. Correlations between pRNFL thinning rate and DR were analyzed using logistic regression. The additive predictive value of the prediction model was assessed using the C-index, net reclassification index (NRI), and integrated discriminant improvement index (IDI).</p><p><strong>Results: </strong>A total of 1012 patients with diabetes (1012 eyes) without DR at both baseline and 1-year follow-up were included in this study. Over the 4-year follow-up, 132 eyes (13%) developed DR. After adjusting for confounding factors, a faster rate of initial pRNFL thinning was significantly associated with the risk of DR (odds ratio per standard deviation [SD] decrease = 1.15, 95% confidence interval [CI] = 1.08 to 1.23, P < 0.001). Incorporating either the baseline pRNFL thickness or its thinning rate into conventional prediction models significantly improved the discriminatory power. Adding the rate of pRNFL thinning further enhanced the discriminative power compared with models with only baseline pRNFL thickness (C-index increased from 0.685 to 0.731, P = 0.040). The IDI and NRI were 0.114 and 0.463, respectively (P < 0.001).</p><p><strong>Conclusions: </strong>The rate of initial pRNFL thinning was associated with DR occurrence and improved discriminatory power of traditional predictive models. This provides new insights into the management and screening of DR.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371857","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}
引用次数: 0
Glial Cell Responses and Gene Expression Dynamics in Retinas of Treated and Untreated RPE65 Mutant Dogs. 经治疗和未经治疗的 RPE65 突变体犬视网膜中神经胶质细胞的反应和基因表达动态。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.18
Tatyana Appelbaum, Evelyn Santana, David A Smith, William A Beltran, Gustavo D Aguirre
{"title":"Glial Cell Responses and Gene Expression Dynamics in Retinas of Treated and Untreated RPE65 Mutant Dogs.","authors":"Tatyana Appelbaum, Evelyn Santana, David A Smith, William A Beltran, Gustavo D Aguirre","doi":"10.1167/iovs.65.12.18","DOIUrl":"10.1167/iovs.65.12.18","url":null,"abstract":"<p><strong>Purpose: </strong>The long-term evaluation of RPE65 gene augmentation initiated in middle-aged RPE65 mutant dogs previously uncovered notable inter-animal and intra-retinal variations in treatment efficacy. The study aims to gain deeper insights into the status of mutant retinas and assess the treatment impact.</p><p><strong>Methods: </strong>Immunohistochemistry utilizing cell-specific markers and reverse transcription-quantitative PCR (RT-qPCR) analysis were conducted on archival retinal sections from normal and RPE65 mutant dogs.</p><p><strong>Results: </strong>Untreated middle-aged mutant retinas exhibited marked downregulation in the majority of 20 examined genes associated with key retinal pathways. These changes were accompanied by a moderate increase in microglia numbers, altered expression patterns of glial-neuronal transmitter recycling proteins, and gliotic responses in Müller glia. Analysis of advanced-aged mutant dogs revealed mild outer nuclear layer loss in the treated eye compared to moderate loss in the corresponding retinal regions of the untreated control eye. However, persistent Müller glial stress response along with photoreceptor synapse loss were evident in both treated and untreated eyes. Photoreceptor synaptic remodeling, infrequent in treated regions, was observed in all untreated advanced-aged retinas, accompanied by a progressive increase in microglial cells indicative of ongoing inflammation. Interestingly, about half of the examined genes showed similar expression levels between treated and untreated advanced-aged mutant retinas, with some reaching normal levels.</p><p><strong>Conclusions: </strong>Gene expression data suggest a shift from pro-degenerative mechanisms in middle-aged mutant retinas to more compensatory mechanisms in preserved retinal regions at advanced stages, despite ongoing degeneration. Such shift, potentially attributed to a number of surviving resilient cells, may influence disease patterns and treatment outcomes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400280","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}
引用次数: 0
TiO2-Nanoparticle-Enhanced Sonodynamic Therapy for Prevention of Posterior Capsular Opacification and Ferroptosis Exploration of Its Mechanism. TiO2-纳米粒子增强声动力疗法用于预防后囊翳和铁沉着症的机制探索
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.24
Yuanyuan Li, Pingjun Chang, Liming Xu, Zehui Zhu, Man Hu, Jiaying Cen, Siyan Li, Yun-E Zhao
{"title":"TiO2-Nanoparticle-Enhanced Sonodynamic Therapy for Prevention of Posterior Capsular Opacification and Ferroptosis Exploration of Its Mechanism.","authors":"Yuanyuan Li, Pingjun Chang, Liming Xu, Zehui Zhu, Man Hu, Jiaying Cen, Siyan Li, Yun-E Zhao","doi":"10.1167/iovs.65.12.24","DOIUrl":"10.1167/iovs.65.12.24","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the application and potential ferroptosis mechanisms of sonodynamic therapy (SDT) using titanium dioxide nanoparticles (TiO2-NPs) as sonosensitizers for the prevention of posterior capsule opacification (PCO).</p><p><strong>Methods: </strong>We fabricated TiO2-NP-coated intraocular lenses (TiO2-IOLs) using the spin-coating method, followed by ultrasound activation of the photosensitizer TiO2. In vitro experiments were performed with human lens epithelial cells (HLECs) to explore the appropriate concentration of TiO2 and ultrasonic parameters. Investigations included reactive oxygen species (ROS) generation, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) western blot analysis, lipid peroxidation assays, and transcriptomics analysis. Finally, TiO2-IOLs were implanted in rabbit eyes to explore the in vivo performance of SDT.</p><p><strong>Results: </strong>Through both in vitro and in vivo experiments, the study determined that the ultrasound parameters of 5-minute duration, 1-MHz frequency, 50% duty cycle, and 1.2-W/cm2 intensity were reliable and valid for killing HLECs without damaging other ocular structures. In vitro experiments demonstrated that SDT generated excess ROS, which disrupted the mitochondrial membrane potential and significantly reduced the GSH content. Additionally, the downregulation of GPX4, accumulation of lipid peroxides, and alteration of mitochondrial morphology were observed, suggesting that ferroptosis may be the underlying mechanism. The RNA-sequencing analysis results also showed an increase in the expression of multiple pro-ferroptosis genes and the ferroptosis marker gene PTGS2. Animal experiments preliminarily demonstrated the safety and effectiveness of SDT in treating PCO in vivo.</p><p><strong>Conclusions: </strong>TiO2-IOLs combined with SDT effectively prevented PCO by generating ROS and intracellular ferroptosis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500051/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465670","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}
引用次数: 0
Multicenter Normative Data for Mesopic Microperimetry. 中焦显微透视测量的多中心规范数据。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.27
Maximilian Pfau, Jasleen K Jolly, Jason Charng, Leon von der Emde, Philipp L Müller, Georg Ansari, Kristina Pfau, Fred K Chen, Zhichao Wu
{"title":"Multicenter Normative Data for Mesopic Microperimetry.","authors":"Maximilian Pfau, Jasleen K Jolly, Jason Charng, Leon von der Emde, Philipp L Müller, Georg Ansari, Kristina Pfau, Fred K Chen, Zhichao Wu","doi":"10.1167/iovs.65.12.27","DOIUrl":"10.1167/iovs.65.12.27","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to provide a large, multi-center normative dataset for the Macular Integrity Assessment (MAIA) microperimeter and compare the goodness-of-fit and prediction interval calibration-error for a panel of hill-of-vision models.</p><p><strong>Methods: </strong>Microperimetry examinations of healthy eyes from five independent study groups and one previously available dataset were included (1137 tests from 531 eyes of 432 participants [223 women and 209 men]). Linear mixed models (LMMs) were fitted to the data to obtain interpretable hill-of-vision models. A panel of regression models to predict normative data was compared using cross-validation with site-wise splits. The mean absolute error (MAE) and miscalibration area (area between the calibration curve and the ideal diagonal) were evaluated as the performance measures.</p><p><strong>Results: </strong>Based on the parameters \"participant age,\" \"eccentricity from the fovea,\" \"overlap with the central fixation target,\" and \"eccentricity along the four principal meridians,\" a Bayesian mixed model had the lowest MAE (2.13 decibel [dB]; 95% confidence interval [CI] = 1.9-2.36 dB) and miscalibration area (0.13; 95% CI = 0.07-0.19). However, a parsimonious linear model provided a comparable MAE (2.17 dB; 95% CI = 1.93-2.4 dB) and a similar miscalibration area (0.14; 95% CI = 0.08-0.2).</p><p><strong>Conclusions: </strong>Normal variations in visual sensitivity on mesopic microperimetry can be effectively explained by a linear model that includes age and eccentricity. The dataset and a code vignette are provided for estimating normative values across a large range of retinal locations, applicable to customized testing patterns.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465684","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}
引用次数: 0
Factors Affecting Stimulus Duration Threshold for Depth Discrimination of Asynchronous Targets in the Intermediate Distance Range. 影响中距离范围内异步目标深度辨别的刺激持续时间阈值的因素。
IF 5 2区 医学
Investigative ophthalmology & visual science Pub Date : 2024-10-01 DOI: 10.1167/iovs.65.12.36
Yiya Chen, Zijiang J He, Teng Leng Ooi
{"title":"Factors Affecting Stimulus Duration Threshold for Depth Discrimination of Asynchronous Targets in the Intermediate Distance Range.","authors":"Yiya Chen, Zijiang J He, Teng Leng Ooi","doi":"10.1167/iovs.65.12.36","DOIUrl":"https://doi.org/10.1167/iovs.65.12.36","url":null,"abstract":"<p><strong>Purpose: </strong>Binocular depth discrimination in the near distance range (< 2 m) improves with stimulus duration. However, whether the same response-pattern holds in the intermediate distance range (approximately 2-25 m) remains unknown because the spatial coding mechanisms are thought to be different.</p><p><strong>Methods: </strong>We used the two-interval forced choice procedure to measure absolute depth discrimination of paired asynchronous targets (3, 6, or 16 arc min). The paired targets (0.2 degrees) were located over a distance and height range, respectively, of 4.5 to 7.0 m and 0.15 to 0.7 m. Experiment 1 estimated duration thresholds for binocular depth discrimination at varying target durations (40-1610 ms), in the presence of a 2 × 6 array of parallel texture-elements spanning 1.5 × 5.83 m on the floor. The texture-elements provided a visible background in the light-tight room (9 × 3 m). Experiment 2 used a similar setup to control for viewing conditions: binocular versus monocular and with versus without texture background. Experiment 3 compared binocular depth discrimination between brief (40, 80, and 125 ms) and continuous texture background presentation.</p><p><strong>Results: </strong>Stimulus duration threshold for depth discrimination decreased with increasing disparity in experiment 1. Experiment 2 revealed depth discrimination performance with texture background was near chance level with monocular viewing. Performance with binocular viewing degraded without texture background. Experiment 3 showed continuous texture background presentation enhances binocular depth discrimination.</p><p><strong>Conclusions: </strong>Absolute depth discrimination improves with target duration, binocular viewing, and texture background. Performance further improved with longer background duration underscoring the role of ground surface representation in spatial coding.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500606","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}
引用次数: 0
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