Investigative ophthalmology & visual science最新文献

{"title":"Quantification of Normative Human Choriocapillaris Measures Across the Macula.","authors":"Daniel X Hammer, Katherine Kovalick, Osamah J Saeedi, Emily Y Chew, Catherine Cukras, Zhuolin Liu","doi":"10.1167/iovs.66.12.26","DOIUrl":"10.1167/iovs.66.12.26","url":null,"abstract":"<p><strong>Purpose: </strong>To assess macular choriocapillaris (CC) metrics in healthy volunteers (HVs) without ocular disease and demonstrate CC variations in patients with inherited retinal dystrophies (IRDs) using adaptive optics optical coherence tomography angiography (AO-OCTA).</p><p><strong>Methods: </strong>Twenty-one HVs and three IRD patients were imaged. Macular variation in 20 HVs in CC metrics (CC density, CC diameter, CC tortuosity, void diameter, void area, lobule count, lobule area, and RPE-CC distance) were assessed by imaging a 28° strip of overlapping AO-OCTA volumes (3° × 3°) from the optic nerve head to the temporal macula. En face projections of the CC at 1° intervals across the strip were created and metrics extracted using custom software.</p><p><strong>Results: </strong>CC density was mostly invariant across the macula at 0.523 ± 0.006, although it was slightly higher in the foveal region. The CC diameter decreased monotonically from 15.9 ± 0.7 µm in the nasal macula (-12°) to 14.2 ± 1.1 µm in the temporal macula (12°). Void measures also decreased from the nasal to the temporal macula: from 16.2 ± 1.4 µm to 14.6 ± 1.2 µm for void diameter and from 1418 ± 436 µm2 to 1243 ± 364 µm2 for void area. Lobule count peaked in the central macula. RPE-CC distance peaked at the fovea (fovea, 16.8 µm; periphery, ∼13-14 µm). CC tortuosity (1.17 ± 0.01) was constant across the macula. We observed a correlation with age in CC density, void diameter, and void area. AO-OCTA detected subclinical flow dropout in drusen regions. CC changes were observed in IRD patients with characteristics specific to the disease.</p><p><strong>Conclusions: </strong>Normative AO-OCTA-based CC metrics can provide insight into ocular disease pathology.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"26"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12429709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145029875","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":"Novel Grm6 Variant in a no b-wave (nob) Mouse Model: Phenotype Characterization and Gene Therapy.","authors":"Pei-Hsuan Lin, Eugene Yu-Chuan Kang, Neoklis Makrides, Winston Lee, Yun-Ju Tseng, Pei-Liang Wu, John Peregrin, Emmet Sherman, Jason Hunghsuan Wang, Theresa C Swayne, Tai-De Li, Melina A Agosto, Janet R Sparrow, Xin Zhang, Stephen H Tsang, Nan-Kai Wang","doi":"10.1167/iovs.66.12.20","DOIUrl":"10.1167/iovs.66.12.20","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize a no b-wave (nob) mouse model of congenital stationary night blindness (CSNB) caused by a Grm6 variant that disrupts photoreceptor-to-bipolar cell signaling. Additionally, we aim to evaluate the efficacy of gene therapy in restoring visual function.</p><p><strong>Methods: </strong>The nob mouse was generated through selective breeding to regenerate the nob phenotype. Adeno-associated viruses encoding Grm6 and GFP, driven by two promoters (hGRM6 and CMV), were administered to nob mice at postnatal days 5 (P5) and 30 (P30), respectively. Electroretinography and spectral domain optical coherence tomography (SD-OCT) were conducted three months after gene therapy.</p><p><strong>Results: </strong>The nob phenotype was successfully regenerated, and a homozygous missense variant c.1037G>A (p.Arg346His) in Grm6 was identified as the causal variant. Scotopic b waves were absent, whereas a waves remained normal, indicating intact rod function but impaired bipolar cell function. SD-OCT revealed thinning of the retinal nerve fiber layer and outer plexiform layer (OPL) in affected mice. Immunofluorescence and immunoblotting revealed decreased mGluR6 levels and associated signaling proteins. Gene therapy restored mGluR6 expression and reestablished synaptic protein localization in the OPL, although improvements in b/a ratios and OPL thickness were modest. Notably, the hGRM6 promoter at P5 was more effective at restoring OPL.</p><p><strong>Conclusions: </strong>We identified a new nob mouse model that mimics the CSNB phenotype in human patients. Whereas gene therapy successfully restored mGluR6 expression, functional improvements were limited. Early treatment using a specific promoter is critical, and increasing transduction efficiency may improve gene therapy strategies.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"20"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023363","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":"Central Bouquet Hemorrhages in Retinal Vein Occlusion: A Distinct Pathway to Macular Atrophy.","authors":"Maria Vittoria Cicinelli, Enrico Maria Pepe, Prithvi Ramtohul, Beatrice Tombolini, Stefano Puligheddu, Alessandro Russo, Francesco Bandello, Rosangela Lattanzio","doi":"10.1167/iovs.66.12.62","DOIUrl":"10.1167/iovs.66.12.62","url":null,"abstract":"<p><strong>Purpose: </strong>To characterize central bouquet hemorrhages (CBHs) in retinal vein occlusion (RVO) and evaluate their association with long-term visual and anatomical outcomes, in particular macular atrophy. This is a retrospective longitudinal cohort study of 403 treatment-naïve eyes with RVO (mean age, 62.9 ± 15.4 years; 59% male).</p><p><strong>Methods: </strong>CBH was identified on spectral-domain optical coherence tomography as vertically oriented light-absorbing masses centered at the fovea, above the external limiting membrane. Clinical characteristics, imaging findings, and intravitreal treatment frequency were compared between eyes with and without CBH. Baseline and longitudinal visual acuity analyzed with multivariable regression models, the prevalence of CBH-related features, and the cumulative incidence and predictors of macular atrophy assessed with Cox regression models were assessed.</p><p><strong>Results: </strong>CBH were observed in 28% of eyes (n = 111) at baseline. Affected eyes were older, had more systemic vascular comorbidities, and presented with more severe macular edema, peripapillary hemorrhages, and cotton-wool spots (all P < 0.001). Ischemic markers-including arteriolar paracentral acute middle maculopathy (P = 0.04) and increased ischemic index on fluorescein angiography (P = 0.02)-were more common in CBH eyes. Over time, CBH reabsorbed, often leaving a plaque-like RPE thickening, which progressed to outer retinal atrophy in 69% of cases over 36 months. Severe cystoid macular edema and full-thickness macular holes were also common. CBH was independently associated with worse baseline visual acuity (β = 0.09 logMAR; 95% confidence interval [CI], 0.01-0.18; P = 0.04) and slower visual recovery (β for CBH × Time = -0.002 logMAR/month; P < 0.001). Intravitreal treatments reduced the risk of macular atrophy (hazard ratio, 0.28; 95% CI, 0.08-0.96; P = 0.04), and each additional injection conferred a protective effect (hazard ratio, 0.96; 95% CI, 0.93-0.99; P = 0.02).</p><p><strong>Conclusions: </strong>CBH represents a characteristic hemorrhagic manifestation in RVO, likely reflecting the localized effects of elevated venous pressure and macular ischemia that contribute to structural disruption and poor visual outcomes. Its presence warrants close monitoring and sustained treatment to mitigate long-term retinal damage.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"62"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145149029","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":"PGC1A Restores Mitochondrial Health to Attenuate EMT During Lens Epithelial Fibrosis via Regulating TFAM.","authors":"Jingqi Huang, Peiyi Jiang, Baoxin Chen, Mi Huang, Jieping Chen, Jiani Wang, Shan Huang, Yizhi Liu","doi":"10.1167/iovs.66.12.67","DOIUrl":"10.1167/iovs.66.12.67","url":null,"abstract":"<p><strong>Purpose: </strong>Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a predominant pathological driver for fibrotic cataracts. This study explores the role and mechanism of peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1A), a key mitochondrial regulator, in EMT of LECs.</p><p><strong>Methods: </strong>RNA-sequencing analysis was applied to reveal biological changes during human lens epithelial fibrosis. Primary rabbit LECs were treated with TGFβ2 to induce EMT. Mitochondrial alterations were evaluated by MitoTracker staining, transmission electron microscopy, mitochondrial membrane potential assay, ATP content assay, and reactive oxygen species (ROS) assay. Loss- and gain-of-function studies were performed to uncover roles and mechanisms of PGC1A in EMT of LECs. Changes of PGC1A, EMT markers, and mitochondrial regulators were analyzed by Western blot, immunofluorescence staining, and RT-qPCR. Cell migration was assessed using the cell scratch assay. Ex vivo whole rat lenses were treated with TGFβ2 to induce fibrotic cataract to evaluate the potential therapeutic effect of PGC1A on lens fibrosis. Lens epithelial fibrosis was examined by hematoxylin and eosin (H&E) and immunofluorescence staining.</p><p><strong>Results: </strong>PGC1A was decreased with significant mitochondrial dysfunction during TGFβ2-induced EMT of LECs. PGC1A silencing promoted EMT by enhancing TGFβ2-Smad2/3 signaling, accelerating subcapsular fibrotic plaque formation. PGC1A upregulation protected LECs from TGFβ2-induced EMT by restoring mitochondrial health and energy metabolism. Mechanistically, PGC1A inhibition decreased mitochondrial transcription factor (TFAM), which mediated protective effects of PGC1A on mitochondria and LECs. Further, ZLN005, a PGC1A agonist, attenuated fibrotic lens opacity via preventing LECs from EMT.</p><p><strong>Conclusions: </strong>PGC1A safeguards LECs against EMT by restoring TFAM-mediated mitochondrial energy metabolism under TGFβ2 stress, offering potential targets for the treatment of lens epithelial fibrosis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"67"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185918","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":"Functional Anatomy of Ocular Counter-Rolling in Superior Oblique Palsy.","authors":"Joseph L Demer, Robert A Clark","doi":"10.1167/iovs.66.12.6","DOIUrl":"10.1167/iovs.66.12.6","url":null,"abstract":"<p><strong>Purpose: </strong>Simulations suggest that displacement of rectus extraocular muscle pulleys in superior oblique (SO) palsy accounts for incomitant strabismus patterns even without postulating SO contractile weakness. We asked how rectus extraocular muscle pulleys reorient during head tilt in SO palsy.</p><p><strong>Methods: </strong>In 13 subjects with unilateral SO palsy, supine magnetic resonance imaging (MRI) in 2-mm-thick quasi-coronal planes in target-controlled central gaze was repeated in both lateral decubitus positions equivalent to 90° head tilts. From extraocular muscle centroids, we computed oculocentric pulley coordinates and compartmental posterior partial volumes (PPVs) of the rectus and SO muscles.</p><p><strong>Results: </strong>Validating atrophy, PPV of the palsied SO was smaller than its fellow (P < 10-4). In fellow orbits, the array of all four rectus pulleys exhibited counter-rotation during head tilt (P < 0.03), averaging 5.9°. The palsied pulley array was in both tilts excyclorotated relative to the fellow orbit, particularly by 4° to 5° for horizontal rectus pulleys (P < 0.03), and also counter-rotated with head tilt similarly to the fellow orbit. Differential compartmental changes in PPV were significant in the lateral and superior rectus and SO muscles of the fellow orbit that were consistent with observed torsion, but were absent in the palsied orbit.</p><p><strong>Conclusions: </strong>Similar counter-rotation of the rectus pulley array during head tilt occurs in both eyes in unilateral SO palsy, but superimposed on excyclorotation of the array in the palsied orbit. Differential compartmental change in PPV occurs during head tilt in the lateral and superior rectus muscles of the fellow but not palsied orbit and could augment ocular counter-rolling.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"6"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954287","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":"Reshaping the Burden of nAMD: National, Regional, and Global Prevalence of MNV3 and Its Correlation With Life Expectancy-The RAP Study, Report 7.","authors":"Bilal Haj Najeeb, Bianca S Gerendas, Stefan Sacu, Oliver Leingang, Gabor Deak, Ursula Schmidt-Erfurth","doi":"10.1167/iovs.66.12.37","DOIUrl":"10.1167/iovs.66.12.37","url":null,"abstract":"<p><strong>Background: </strong>To report the global distribution of macular neovascularization type 3 (MNV3) and to redefine the associated burden of neovascular age-related macular degeneration (nAMD).</p><p><strong>Methods: </strong>A total of 4652 patients with treatment-naïve nAMD were included. MNV3 was diagnosed using multimodal imaging methods. The prevalence of MNV3 in each country, region, continent and worldwide was calculated. The correlation between the prevalence of MNV3 and life expectancy in each country was estimated. Continent prevalence data was compared using a logistic (binomial) generalized linear mixed model (GLMM).</p><p><strong>Results: </strong>Our analysis revealed 4652 nAMD eyes from 47 countries, 575 (12.4%) of which had MNV3. In North America, the highest percentage was in Canada (17.6%), followed by the USA (11.5%). In Europe, the highest prevalence (23.4%) was in Austria and the lowest (4.3%) in Russia and Croatia. The prevalence in Asia, South America, and Australia was 6.6%, 9.4%, and 13.7%. A significant positive correlation was found between the MNV3 prevalence and life expectancy in 20 European countries (r = 0.63, P < 0.003). The GLMM revealed significantly lower odds for observing MNV3 in Asia compared to Europe (P < 0.01). No significant difference was observed in any other continent pair. The prevalence in Western Europe and Mediterranean region was higher than in Eastern Europe and the non-Mediterranean region (18.6% vs. 9.6%, P < 0.001; and 17.5% vs. 12.6%, P = 0.001, respectively).</p><p><strong>Conclusions: </strong>MNV3 is more prevalent in Western and Mediterranean regions, likely because of higher life expectancy and a lower percentage of Asian ethnicity. AREDS supplements and the Mediterranean diet may not provide prophylactic benefits against the development of MNV3. The unique distribution pattern of MNV3 and its correlation with life expectancy should be considered in nAMD research to ensure adequate representation of MNV3 patients in clinical trials.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"37"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12449815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075256","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":"Evaluation of Reflectivities of RPE, ELM, EZ, and Their Relationship With Subretinal Fluid Properties in Central Serous Chorioretinopathy.","authors":"Ekin Ece Oskan, Abdullah Agin, Mine Ozturk, Feyza Onder","doi":"10.1167/iovs.66.12.19","DOIUrl":"10.1167/iovs.66.12.19","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to assess the reflectivity of the outer retinal layers (ORLs) in patients with central serous chorioretinopathy (CSCR) and to examine the relationship between the dimensions of the subretinal fluid (SRF) and ORL.</p><p><strong>Methods: </strong>This retrospective, cross-sectional study included 33 eyes of 33 patients with CSCR and 33 age- and gender-matched controls. Unnormalized and relative reflectivities for the retinal pigment epithelium (RPE), the external limiting membrane (ELM), and the ellipsoid zone (EZ), as well as SRF height, base width, and area, were measured on optical coherence tomography images. Reflectivity measurements for each retinal layer were performed at three anatomic locations (foveal center, nasal, and temporal regions, 1 mm apart), and the average of these three values was used to calculate average reflectivity (RPEav, EZav, ELMav).</p><p><strong>Results: </strong>RPEav, EZav, and ELMav were lower in patients with CSCR (P < 0.001). In the pigment epithelium detachment (PED) group, EZn and EZav were significantly lower than in the non-PED group (P = 0.012 and P = 0.013, respectively). A negative correlation was observed between SRF base width and EZav (P = 0.018) and ELMav (P = 0.021). SRF area was negatively correlated with both EZav (P = 0.049) and ELMav (P = 0.025). RPEc was negatively correlated with SRF elevation (P = 0.016).</p><p><strong>Conclusions: </strong>This study reveals novel associations between SRF dimensions, PED presence, and outer retinal layer damage in CSCR. Monitoring ORL reflectivity changes may provide insights into disease pathogenesis and help evaluate treatment efficacy.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"19"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12422389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145015362","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":"Integrative Multiomics Identifies CD64⁺ Monocytes as Potential Contributors to Age-Related Macular Degeneration.","authors":"Cunzi Li, Lan Zhou, Tianyi Luo, Hongyan Sun, Ruirui Ma, Jun Wang, Ming-Ming Yang","doi":"10.1167/iovs.66.12.32","DOIUrl":"10.1167/iovs.66.12.32","url":null,"abstract":"<p><strong>Purpose: </strong>Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly, characterized by chronic retinal inflammation and immune dysregulation. While myeloid cells have been increasingly implicated in AMD pathogenesis, the specific immune subsets responsible remain poorly defined. This study aimed to identify causal immune cell populations and elucidate their functional roles in AMD progression.</p><p><strong>Methods: </strong>We employed an integrative multiomics strategy encompassing Mendelian randomization (MR) analysis using genome-wide association study summary statistics, single-cell RNA sequencing (scRNA-seq) analysis of retinal pigment epithelium (RPE)/choroid tissues from patients with AMD and healthy controls (GSE230348), and flow cytometric (FCM) validation in a sodium iodate-induced dry AMD mouse model.</p><p><strong>Results: </strong>MR analysis identified a significant causal association between CD64 expression on CD14⁻CD16⁻ monocytes and increased AMD risk (odds ratio, 1.179; P < 0.001). scRNA-seq profiling revealed a pronounced enrichment of CD14⁻CD16⁻ monocytes in AMD tissues, with FCGR1A (CD64) expression specifically localized within this subset. Pseudotime trajectory analysis demonstrated dynamic activation and differentiation states among monocyte populations in AMD. Ligand-receptor interaction modeling identified three major signaling pathways, MIF-CD74-CXCR4, IGF1-IGF1R, and SEMA3C-PLXND1, mediating interactions between CD14⁻CD16⁻ monocytes and RPE cells. FCM analysis of retinal single-cell suspensions in AMD mice confirmed a significantly higher proportion of CD64⁺ myeloid cells compared to controls.</p><p><strong>Conclusions: </strong>This study identifies CD64⁺CD14⁻CD16⁻ monocytes as potential contributors to AMD and reveals their putative immunomodulatory crosstalk with RPE cells. These findings highlight CD64 as a promising biomarker and therapeutic target for mitigating myeloid-driven inflammation in AMD.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"32"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12442939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064534","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":"Methylphenidate Inhibits the Development of Myopia by Altering Dopamine and Norepinephrine Reuptake.","authors":"Cindy Karouta, Kate Thomson, Ian Morgan, Lauren Booth, Regan Ashby","doi":"10.1167/iovs.66.12.52","DOIUrl":"10.1167/iovs.66.12.52","url":null,"abstract":"<p><strong>Purpose: </strong>Dopaminergic dysregulation plays a critical role in myopia development in animal models. Although its relevance to human myopia remains uncertain, the observation that methylphenidate hydrochloride (MPH)-a dopamine (DA) and norepinephrine (NE) uptake inhibitor-slows myopia progression in children suggests a possible link. This study aimed to investigate whether MPH can inhibit myopic growth and elucidate the underlying mechanisms using an animal model.</p><p><strong>Methods: </strong>MPH was administered via oral, topical, or intravitreal routes for 7 days (minimum 5 per group) to chicks undergoing form-deprivation myopia (FDM). Myopia was assessed by refraction and axial length. Retinal DA and NE dynamics-including synthesis, release, uptake, breakdown (DA only), extracellular levels, and receptor sensitivity-were evaluated using mass spectrometry and chronoamperometry (minimum 5 per group). DA and NE receptors were pharmacologically blocked (DA = spiperone, SCH-23390; and NE = yohimbine) to determine their role in MPH's anti-myopic effects.</p><p><strong>Results: </strong>MPH inhibited FDM via all administration routes (oral = 55%, P < 0.05, topical = 45%, P < 0.05, and intravitreal = 87%, P < 0.05 protection against myopic growth). It enhanced DA and NE synthesis while blocking their uptake, resulting in elevated extracellular levels. MPH's anti-myopic effects were abolished when DA or NE receptors were pharmacologically blocked. Additionally, NE receptor stimulation alone inhibited FDM (P < 0.05).</p><p><strong>Conclusions: </strong>MPH suppresses experimental myopia, with its effects linked to increased extracellular levels of DA and NE. These findings align with the anti-myopic effects observed in clinical studies, supporting a role for DA in human myopia and suggesting that NE may also contribute to the regulation of ocular growth.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"52"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124728","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":"Elevated Nasal-Temporal Asymmetry of the Choroidal Vascular Index in Pathologically Myopic Eyes.","authors":"Xuewen Ding, Yiyi Wang, Ni Wan, Xiaotian Wu, Jieying Shen, Haiyao Wang, Kuangching Lin, Hao Chen, Tong Wang, Ning Xu, Jinsong Wang, Meixiao Shen, Yanfeng Jiang, Fan Lu, Yilei Shao","doi":"10.1167/iovs.66.12.66","DOIUrl":"10.1167/iovs.66.12.66","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate regional variations in choroidal parameters and to assess whether intraocular symmetry can aid in identifying pathological myopia.</p><p><strong>Methods: </strong>Optical coherence tomography (OCT) images were analyzed from 53 eyes with non-high myopia (NHM), 30 eyes with simple high myopia (HM), and 29 eyes with pathological myopia (PM). Choroidal thickness (CT), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI) were measured within a 6 mm diameter macular region centered on the fovea. Intraocular symmetry of choroidal parameters was quantified by calculating absolute differences between the nasal and temporal, as well as the superior and inferior, regions. These measurements were combined with existing clinical data to help distinguish pathological myopia.</p><p><strong>Results: </strong>In the PM group, CT, LA, and SA were significantly reduced compared to both the HM and NHM groups (P < 0.001). The CVI in eyes with pathological myopia showed intergroup differences in certain areas when compared to eyes with NHM and/or simple HM. As myopia progresses, nasal-temporal CVI symmetry tends to increase in high myopia but decreases in pathological myopia. A model that included intraocular symmetry parameters demonstrated an impressive discriminative ability with an area under the curve value of 0.970 in distinguishing eyes with PM from those with HM.</p><p><strong>Conclusions: </strong>Our findings indicate that PM is characterized by topographical changes in CVI and a reduction in intraocular symmetry, which enhances its differentiation from simple HM.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 12","pages":"66"},"PeriodicalIF":4.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12489860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145185890","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}