Investigative ophthalmology & visual science最新文献

{"title":"Detailed Clinical, Ophthalmic, and Genetic Characterization of MYO7A-Associated Usher Syndrome.","authors":"Juan C Romo-Aguas, Thales A C de Guimarães, Angelos Kalitzeos, Nancy Aychoua, Chrysanthi Tsika, Anthony G Robson, Yu Fujinami-Yokokawa, Kaoru Fujinami, Omar A Mahroo, Andrew R Webster, Michel Michaelides","doi":"10.1167/iovs.66.4.60","DOIUrl":"https://doi.org/10.1167/iovs.66.4.60","url":null,"abstract":"<p><strong>Purpose: </strong>To analyze the clinical spectrum and natural history of MYO7A-associated Usher syndrome type I (USH1).</p><p><strong>Methods: </strong>Patients with molecularly confirmed MYO7A-associated USH1 in a single tertiary referral center. Data was extracted from physical and electronic case notes, including imaging and electrophysiology. Genetic results were reviewed, and the detected variants were assessed. Main outcome measures were clinical findings, qualitative and quantitative analysis of retinal imaging, and electrophysiology.</p><p><strong>Results: </strong>Eighty patients were identified and evaluated longitudinally. The mean age (±SD) of onset of symptoms was 12.0 ± 5.8 years of age, and a mean follow-up time of 16.2 years. BCVA was 0.4 ± 0.5 LogMAR at baseline, and 0.7 ± 0.8 LogMAR at the last visit for both eyes. The change in BCVA over time was 0.02 LogMAR per year. A hyperautofluorescent (hyperAF) ring was present in 51% of the patients. The mean ellipsoid zone width (EZW) at baseline was 2568.2 ± 1528.9 µm OD and 2527.9 ± 1609.3 µm OS, which decreased to 2012.3 ± 1705.1 µm OD and 1806.3 ± 1647.1 µm OS at last visit. Electrophysiology revealed rod and cone dysfunction with relative or complete sparing of macular function. There were statistically significant changes in BCVA, EZW, and hyperAF ring between baseline and follow-up. Genetic analysis identified 83 variants in MYO7A, including 18 novel variants.</p><p><strong>Conclusions: </strong>Longitudinal analysis shows that the majority of patients retain central visual function and structure until the fifth decade of life, which informs advice on prognosis and the window for therapeutic intervention.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"60"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965176","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":"Conjunctival MicroRNA Expression Signature in Primary Sjögren's Syndrome Dry Eye: A NanoString-Based Bioinformatic Analysis.","authors":"Francesca Giovannetti, Paola Pontecorvi, Francesca Megiorni, Marta Armentano, Ludovico Alisi, Enrico Romano, Cinzia Marchese, Alessandro Lambiase, Alice Bruscolini","doi":"10.1167/iovs.66.4.80","DOIUrl":"https://doi.org/10.1167/iovs.66.4.80","url":null,"abstract":"<p><strong>Purpose: </strong>Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease characterized by inflammation and tissue destruction of the salivary and lacrimal glands, leading to sicca symptoms. Dysregulation of microRNAs (miRNAs), key post-transcriptional regulators, has been implicated in pSS, but their role in conjunctival epithelial cells (CECs) remains unclear. This study aimed to identify altered miRNA expression patterns in CEC from patients with pSS and their potential involvement in pSS pathogenesis.</p><p><strong>Methods: </strong>CEC samples were collected from six patients with pSS and six healthy controls (HCs) using nylon-tipped swabs. The miRNA expression was profiled using the NanoString nCounter system with minimal RNA input. Differentially expressed (DE) miRNAs were identified via ROSALIND software, and bioinformatics tools (miRNet and miRTargetLink) were applied to construct miRNA-centric networks, predict target genes, and perform pathway enrichment analysis.</p><p><strong>Results: </strong>We identified 11 DE miRNAs in patients with pSS compared with the HCs. Key miRNAs, including hsa-miR-548j-3p and hsa-miR-219b-3p, are central to immune and inflammatory regulation pathways. Pathway enrichment analysis highlighted their involvement in processes such as immune cell regulation, inflammatory signaling, and glandular damage. Dysregulated miRNAs modulate key targets, like TNFAIP3, IL6R, IFNAR1, IL7, and ICOSLG, suggesting their potential role in pSS pathogenesis.</p><p><strong>Conclusions: </strong>This study underscores the potential of miRNAs as biomarkers and therapeutic targets in pSS-associated dry eye disease. Despite limitations like small sample size and reliance on in silico predictions, our findings provide valuable insights into miRNA-mediated regulation of immune responses and inflammation, paving the way for future diagnostic and therapeutic advancements.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"80"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000500","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":"Microglia-Derived IL-6 Promotes Müller Glia Reprogramming and Proliferation in Zebrafish Retina Regeneration.","authors":"Jie Xu, Yi Li, Xiangyu Li, Xuan Tan, Lihua Liu, Lining Cao, Hui Xu","doi":"10.1167/iovs.66.4.67","DOIUrl":"https://doi.org/10.1167/iovs.66.4.67","url":null,"abstract":"<p><strong>Purpose: </strong>Inflammation activates the Jak1-Stat3 signaling pathway in zebrafish Müller glia (MG), leading to their status transition and proliferation following retinal injury. However, the source of Stat3-activating molecules remains unclear. This study aims to explore the expression and function of a Stat3-activating cytokine IL-6 in zebrafish retina regeneration.</p><p><strong>Methods: </strong>Mechanical retinal injury was induced in adult zebrafish by a needle-poke lesion. Single-cell RNA sequencing (scRNAseq) and PCR were used to determine gene expression. Microglia ablation was performed by using the mpeg1:nsfb-mcherry transgenic zebrafish. Morpholino oligonucleotides, a recombinant zebrafish IL-6 protein and drugs, were used to manipulate IL-6 or Stat3 signaling in the retina. The 5-Ethynyl-2'-deoxyuridine (EdU) labeling was used to evaluate MG proliferation and the formation of MG-derived progenitor cells (MGPCs). Neuronal regeneration in the retina was analyzed by lineage tracing and immunostaining.</p><p><strong>Results: </strong>The scRNAseq reveals that IL-6 is mainly expressed by a subset of pro-inflammatory microglia in the injured retina. Loss- and gain-of-function experiments demonstrate that IL-6 signaling promotes MG proliferation and the formation of MGPCs following retinal injury. Additionally, IL-6 facilitates MG status transition by modulating Jak1-Stat3 signaling and the expression of regeneration-associated genes. Interestingly, IL-6 may also regulate MGPC formation via phase-dependent pro-inflammatory and anti-inflammatory mechanisms. Finally, IL-6 promotes the early differentiation of MGPCs and contributes to the regeneration of retinal neurons in the injured retina.</p><p><strong>Conclusions: </strong>Our study unveils the critical role of microglia-derived IL-6 in zebrafish retina regeneration, with potential implications for mammalian MG reprogramming.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"67"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12025339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063842","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":"CD4+CD25- T-Cell-Secreted IFN-γ Promotes Corneal Nerve Degeneration in Diabetic Mice.","authors":"Yujing Lin, Lingling Yang, Ya Li, Shengqian Dou, Zhenzhen Zhang, Qingjun Zhou","doi":"10.1167/iovs.66.4.15","DOIUrl":"10.1167/iovs.66.4.15","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to explore the relationship between corneal nerve degeneration and elevated dendritic cells (DCs) in diabetic keratopathy.</p><p><strong>Methods: </strong>Corneas from diabetic and healthy mice were analyzed using single-cell RNA sequencing. Corneal nerve density and DC and T-cell infiltration were quantified through whole-mount corneal staining. Freshly isolated mouse trigeminal ganglion (TG) neurons were co-cultured with immature DCs, mature DCs, activated CD8+ T cells, and CD4+CD25- T cells. TG neurite outgrowth was assessed to identify potential effector cells driving corneal nerve degeneration. In addition, interferon-gamma (IFN-γ) and blocking antibodies were used to evaluate their effects on TG neurite outgrowth and corneal nerve degeneration in mice.</p><p><strong>Results: </strong>Compared with age-matched healthy mice, diabetic mice exhibited a significant reduction in corneal nerve density and sensitivity, along with increased infiltration of DCs, CD4+ T cells, and CD8+ T cells. In vitro co-culture experiments revealed that CD4+CD25- T cells, rather than DCs and CD8+ T cells, significantly inhibited TG neurite outgrowth. Among cytokines, elevated IFN-γ in diabetic corneas impaired TG neurite outgrowth and induced corneal nerve degeneration, whereas IL-4 and IL-17 had no such effect. Blocking IFN-γ alleviated CD4+CD25- T-cell-induced inhibition of TG neurite outgrowth and corneal nerve degeneration in diabetic mice.</p><p><strong>Conclusions: </strong>CD4+CD25- T cells, but not DCs or CD8+ T cells, contribute to corneal nerve degeneration in diabetic mice, a process partially mediated by IFN-γ.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"15"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11980951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795504","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":"In Vivo Brillouin Analysis of Lens Nucleus and Cortex in Adult Myopic Eyes and Their Correlation With Accommodation.","authors":"Le Chang, Fen Song, Shijia Qu, Huazheng Cao, Yanan Wu, Lulu Xu, Jing Wang, Ruirui Zhang, Chao Xue, Yan Wang","doi":"10.1167/iovs.66.4.6","DOIUrl":"10.1167/iovs.66.4.6","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the in vivo biomechanical properties of crystalline lens nucleus and cortex in adults with myopia, their potential influences, and the correlation between these properties and ocular accommodation.</p><p><strong>Methods: </strong>The study included 195 right eyes of 195 participants, divided into 4 groups based on spherical equivalent: emmetropia (37 eyes), low myopia (41 eyes), moderate myopia (59 eyes), and high myopia (58 eyes). Participants underwent comprehensive ophthalmological examinations, including intraocular pressure, axial length, cycloplegic refraction, lens morphology, accommodation measurements, and Brillouin optical scanning of the lens. Additionally, demographic information, such as age and sex, was recorded. Normality tests were performed on the data using the Kolmogorov-Smirnov test. Between-group differences were examined using the Kruskal-Wallis test. Correlation and multiple regression analyses were conducted to analyze the factors associated with lens biomechanical properties and accommodation.</p><p><strong>Results: </strong>The mean longitudinal modulus of the crystalline lens nucleus (LMN), anterior cortex (LMAC), and posterior cortex (LMPC) was 3.395 ± 0.027 GPa, 3.030 ± 0.066 GPa, and 2.990 ± 0.066 GPa, respectively, in adult myopia and 3.342 ± 0.024 GPa, 3.015 ± 0.0488 GPa, and 2.978 ± 0.049 GPa, respectively, in emmetropia. LMN was significantly higher in myopia (difference = 0.047, 95% confidence interval [CI] = 0.037 to 0.057, P < 0.001) and increased significantly with higher degrees of myopia (standardized β = -0.712, P < 0.001). No statistical differences in the LMAC or LMPC were observed between myopia and emmetropia. Lens densitometry on the centerline was the only lens parameter independently correlated with LMN (standardized β = -0.282, P < 0.01). Increased LMN in myopia was independently correlated with increased amplitude of accommodation (AMP) and decreased accommodative facility (AF; standardized β = 0.198, -0.237, all P < 0.05).</p><p><strong>Conclusions: </strong>LMN was significantly higher in adult patients with myopia than in emmetropia and increased with increasing myopia. Increased LMN in myopia significantly correlated with decreased AF and increased AMP. High LMN may be an important biological alteration during the development of adult myopia, especially high myopia, providing new insights into myopia pathogenesis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"6"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763173","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":"Targeted Neuroprotection of Retinal Ganglion Cells Via AAV2-hSyn-NGF Gene Therapy in Glaucoma Models.","authors":"Xinlei Zhu, Benxiang Qi, Zhongmei Ren, Lin Cong, Xiaojing Pan, Qingjun Zhou, Bi Ning Zhang, Lixin Xie","doi":"10.1167/iovs.66.4.48","DOIUrl":"https://doi.org/10.1167/iovs.66.4.48","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to evaluate the neuroprotective effects of delivering nerve growth factor (NGF) to retinal ganglion cells (RGCs) through adeno-associated virus serotype 2 (AAV2) carrying a neuronal-specific human synapsin (hSyn) promoter.</p><p><strong>Methods: </strong>AAV2-hSyn-NGF was injected intravitreally in three glaucoma models: optic nerve crush (ONC), microbead-induced ocular hypertension (MB), and genetic glaucoma model (DBA). Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) determined the optimal injection concentration of AAV vector. Flow cytometry monitored immune responses. Transduction efficiency was quantified using green fluorescent protein (GFP) co-localization with RGC-specific marker RNA-binding protein with multiple splicing (RBPMS). The RGCs' density, retinal nerve fiber density, ganglion cell complex thickness, and positive scotopic threshold response (pSTR) were measured to assess structural and functional outcomes of the RGCs. Non-parametric Mann-Whitney U tests or Kruskal-Wallis tests were utilized to ascertain the statistical significance (P < 0.05).</p><p><strong>Results: </strong>The optimal concentration of AAV vector for intravitreal injection was determined to be 1 × 1010 vector particles (VPs) per eye. The use of the hSyn promoter significantly enhanced targeting specificity to RGCs, resulting in a transduction efficiency of 46.64% ± 2.18%. Administration of AAV2-hSyn-NGF effectively preserved the RGCs' density, nerve fiber layer integrity, and the thickness of ganglion cell complex, while maintaining the RGCs' function across three glaucoma models. Furthermore, this gene delivery system did not elicit detectable immune responses or structural damage to the retina.</p><p><strong>Conclusions: </strong>The AAV2-hSyn-NGF gene therapy offers a safe and effective neuroprotective strategy for RGCs across multiple glaucoma models, making it a promising candidate for future clinical trials in patients with glaucoma.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"48"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143996685","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":"Motion Misperception in Anisomyopia Before and After Optical Correction.","authors":"Mengting Chen, Jian Li, Nan Jiang, Jiawei Zhou, Seung Hyun Min","doi":"10.1167/iovs.66.4.71","DOIUrl":"https://doi.org/10.1167/iovs.66.4.71","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate interocular delay in anisomyopes at different spatial frequencies.</p><p><strong>Methods: </strong>Interocular delay (difference in processing speeds between eyes) was measured psychophysically in 21 anisomyopes (observers with a large refractive difference), 20 isomyopes, and 19 emmetropes at 0.5, 1, and 2 cycles per degree (c/deg). During the visual task, small Gabor elements with lateral movements were shown to both eyes. When interocular delay was present, the stimuli created an illusory percept of a cylinder rotating in depth (motion misperception) despite no depth cues. Anisomyopes and isomyopes were tested before and after optical correction; emmetropes were tested only before. Clinical differences between eyes in anisomyopes, including axial length, visual acuity, and spherical equivalent, were also measured.</p><p><strong>Results: </strong>Anisomyopes showed interocular delay at 2 c/deg, with the more myopic eye faster before optical correction (Cohen's d = 0.48), correlating with clinical differences (P < 0.05). Optical correction abolished this delay at 2 c/deg. At 0.5 and 1 c/deg, anisomyopes showed no delay before optical correction, although there were spatial differences between the eyes. Surprisingly, they showed interocular delay after optical correction (more myopic eye faster) when the images of both eyes were spatially equal (P < 0.05). Isomyopes and emmetropes showed no interocular delay at any spatial frequency before and after optical correction.</p><p><strong>Conclusions: </strong>Anisomyopes experience motion misperception at 2 c/deg before optical correction and at 0.5 and 1 c/deg after correction, suggesting optical and neural origins of interocular delay. Tailored interventions based on clinical characteristics may help improve visual function such as motion perception.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"71"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12032845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015809","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":"Assessment of Ocular Magnification in Relation to Biometric Parameters and Measurement Techniques: A Prospective Study.","authors":"Serhat Ermis, Ece Özal, Emrullah Simsek, Özlem Tastan, Murat Karapapak","doi":"10.1167/iovs.66.4.57","DOIUrl":"https://doi.org/10.1167/iovs.66.4.57","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to evaluate the effects of factors such as axial length (AL), spherical equivalent (SE), and keratometry (K) on longitudinal and lateral magnification and their impact on Bruch's membrane opening (BMO)-fovea distance and central foveal thickness (CFT) measurements.</p><p><strong>Methods: </strong>This prospective cross-sectional study included 437 eyes of 437 healthy participants aged 18 to 50 years with best corrected visual acuity of 20/20 or better. Participants were divided into three groups according to their refractive status: myopia (< -0.50 diopters [D]), emmetropia (-0.50 to +0.50 D), and hypermetropia (>+0.50 D). BMO-fovea distance and CFT were measured using a Topcon swept-source optical coherence tomography SS-OCT device, first without taking into account the magnification of the eye and then by incorporating individual AL, SE, and K into the system. Measurement errors greater than 5% were considered significant.</p><p><strong>Results: </strong>Longitudinal and lateral magnification affected BMO-fovea distance and CFT differently. Image size correction was required in 60% of BMO-fovea and 41% of CFT measurements. BMO-fovea distance was significantly influenced by lateral magnification, whereas CFT remained largely unchanged, indicating its primary association with longitudinal magnification. The highest correction need was observed in hypermetropic (87.7%) and short AL eyes (66.1%).</p><p><strong>Conclusions: </strong>It has been demonstrated that BMO-fovea distance is sensitive to lateral magnification, whereas CFT is mainly affected by longitudinal magnification. Neglecting these effects, particularly in hypermetropic and short AL eyes, may lead to significant measurement errors. These findings highlight the necessity of considering both longitudinal and lateral magnification corrections in retinal imaging.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"57"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12020948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997107","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":"Proliferator-Activated Receptor Alpha Inhibits Abnormal Extracellular Matrix Accumulation and Maintains Energy Metabolism in Late-Onset Fuchs Endothelial Corneal Dystrophy.","authors":"Xiaoqi Li, Anqi Liu, Yannan Zhou, Haolan Qi, Junyi Wang, Mingxiong Chen, Tunan Sun, Jie Wu, Yifei Huang, Liqiang Wang","doi":"10.1167/iovs.66.4.36","DOIUrl":"https://doi.org/10.1167/iovs.66.4.36","url":null,"abstract":"<p><strong>Purpose: </strong>Fuchs endothelial corneal dystrophy (FECD) is the most common corneal endothelial dystrophy and guttae are crucial in causing progressive loss of corneal endothelium. This study aimed to find a way to inhibit the formation of guttae in FECD.</p><p><strong>Methods and results: </strong>Mitochondria fatty acid β-oxidation (FAO) and tricarboxylic acid (TCA) cycle processes were negatively enriched in the FECD group according to gene set enrichment analysis in GSE171830. In vivo UV-A-induced late-onset FECD mouse model were established. After irradiation, aged proliferator-activated receptor alpha (PPARα-/-) mice manifested greater corneal opacity, cornea edema, and varied corneal endothelial cell morphology compared with wild-type mice. The total metabolites in cornea of aged PPARα-/- mice and wild-type mice were detected by mass spectrometry. Metabolites of the FAO pathway were decreased in corneas of PPARα-/- mice, coincident with enzymes of FAO decreased in GSE171830. The score for FAO energy metabolism was negatively related to that of the TGF-β pathway according to gene set variation analysis. The express of alpha smooth muscle actin (αSMA) and Col1a were increased in aged PPARα-/- mice and small interfering PPARα B4G12 cell lines. After irradiation, activation or overexpression of PPARα demonstrated reduced corneal endothelial damage and reversal of Descemet membrane thickening, along with downregulation of fibrosis-related genes such as αSMA and collagen type I alpha 1 (Col1a). In vitro experiments revealed that fenofibrate could reverse fibrosis and damage of cell-to-cell connections induced by TGF-β. Additionally, fenofibrate was found to alleviate mitochondrial damage in B4G12 and increase oxygen consumption rates after TGF-β treatment.</p><p><strong>Conclusions: </strong>Overall, we suggested that the overexpression or activation of PPARα can inhibit FAO energy dysfunction of corneal endothelium and the abnormal extracellular matrix formation in Descemet's membrane, which is the primary pathology of FECD. Thus, PPARα may be a potential target for attenuating the progression of FECD.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"36"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983896","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 Contour Integration Deficits in Children With Amblyopia.","authors":"Yan-Ru Chen, Shu-Qi Jiang, Xiang-Yun Liu, Jun-Yun Zhang","doi":"10.1167/iovs.66.4.27","DOIUrl":"https://doi.org/10.1167/iovs.66.4.27","url":null,"abstract":"<p><strong>Purpose: </strong>Contour integration, the process of combining local visual fragments into coherent paths or shapes, is essential for visual perception. Although prior research on amblyopia has focused primarily on spatial domain deficits in contour integration, this study investigates how amblyopia affects contour integration over time and examines the relationship between temporal contour integration deficits and visual functions.</p><p><strong>Methods: </strong>Nineteen amblyopic children (mean age, 10.9 ± 2.4 years; 17 anisometropic, 2 anisometropic/strabismic mixed) and 26 visually normal children (mean age, 10.5 ± 1.8 years) participated in this study. Temporal contour integration was assessed by measuring the accuracy of detecting tilted contour paths, formed by collinear Gabor elements with similar orientations, under slit-viewing conditions. Performance was evaluated for amblyopic eyes (AEs) and fellow eyes (FEs) at two spatial frequencies (1.5 cpd and 3 cpd). The slit width, orientation jitter of contour elements, and stimulus movement speed were systematically varied across separate runs. Visual acuity and Randot stereoacuity were assessed before testing.</p><p><strong>Results: </strong>AEs exhibited significant deficits in temporal contour processing compared with FEs. Specifically, AEs required larger slit widths to achieve performance levels comparable to FEs, with more severe amblyopia (i.e., worse AE visual acuity) necessitating even larger slit widths for temporal contour integration. Temporal contour integration deficits in AEs were most pronounced under conditions of complete Gabor collinearity or moderate stimulus movement speeds (6.4°/s). No significant differences were observed between FEs and control eyes. Notably, the temporal contour integration ability between the two eyes quantified as the AE/FE ratio of slit width thresholds showed no correlation with interocular acuity differences, stereoacuity, or spatial contour integration deficits.</p><p><strong>Conclusions: </strong>Amblyopic children demonstrate significant deficits in temporal contour integration in AEs, which seem to be independent of spatial contour integration deficits. The severity of these temporal deficits increases with worse AE visual acuity. These findings suggest that amblyopia is associated with temporal deficits in visual integration, in addition to the well-documented spatial deficits, highlighting the need for a more comprehensive understanding of amblyopic visual processing.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 4","pages":"27"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12005446/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003344","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}