Investigative ophthalmology & visual science最新文献

{"title":"How Have Animal Models Increased our Understanding of Human Myopia?","authors":"Mark A Bullimore","doi":"10.1167/iovs.66.7.2","DOIUrl":"10.1167/iovs.66.7.2","url":null,"abstract":"<p><p>The extent to which animal models of refractive development have increased our understanding of human myopia is reviewed. During postnatal development refractive errors converge on emmetropia in young animals but form deprivation disrupts this process. Their eyes compensate for optically imposed myopic or hyperopic defocus and recover from the induced refractive error when form deprivation or optical defocus is removed. All of these features have, to some extent, been observed in young children. The lens paradigm has been further leveraged in animals to investigate the influence of competing optical signals on refractive error. These, in turn, have informed and validated certain myopia control technologies. Short-term choroidal thickening and thinning can be induced by positive and negative lenses, respectively, in both animals and humans, although these changes are much smaller and more variable in the latter. Finally, inconsistencies among animal models, inconsistencies between animal models and human myopia, and knowledge gaps and opportunities are discussed.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 7","pages":"2"},"PeriodicalIF":5.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225491","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":"Childhood Myopia Part II: Treatment Mechanisms, Emerging Options, and Considerations.","authors":"Safal Khanal, Erin S Tomiyama, Síofra C Harrington","doi":"10.1167/iovs.66.7.7","DOIUrl":"10.1167/iovs.66.7.7","url":null,"abstract":"<p><p>The rapidly increasing prevalence of myopia and its association with vision-threatening complications in later life has intensified efforts to identify treatments that can prevent the onset and slow the progression of myopia in children. These efforts have led to the development of several optical, environmental, and pharmacological myopia control treatments. Investigations of additional treatment options are ongoing and have shown great promise for clinical translation. Although significant progress has been made in identifying potential pathways and modes of action of these treatments, a complete mechanistic understanding is still lacking. This critical review article explores the potential mechanisms underlying the myopia control effects of contemporary treatments for childhood myopia. It also provides an evidence-based overview of emerging and experimental myopia control therapies. Additionally, the article addresses key considerations, including patient-related factors, treatment limitations, clinical trial designs, efficacy, and cost-effectiveness. This article is the second part of the commissioned paper \"Treatment of Childhood Myopia\" submitted to the National Academies of Sciences, Engineering, and Medicine for the consensus study Focus on Myopia-Pathogenesis and Rising Incidence. For a comprehensive overview of contemporary treatments for childhood myopia in and outside the United States, readers are referred to Childhood Myopia Part I: Contemporary Treatment Options. The findings in this review article underscore the need for continued research to deepen our understanding of the mechanisms underlying myopia treatments, evaluate the long-term safety and efficacy of current and emerging therapies, and identify patient- and treatment-related factors to optimize treatment outcomes in the clinical care of children with myopia.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 7","pages":"7"},"PeriodicalIF":5.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225490","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":"The Multifaceted Landscape of Myopia: Exploring Animal Models, the Optical and Visual Diet, Genetic and Environmental Factors, Access to Care, and Treatment Approaches.","authors":"Tina M Winters, Molly Checksfield Dorries","doi":"10.1167/iovs.66.7.1","DOIUrl":"10.1167/iovs.66.7.1","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 7","pages":"1"},"PeriodicalIF":5.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225506","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":"Childhood Myopia Part I: Contemporary Treatment Options.","authors":"Safal Khanal, Erin S Tomiyama, Síofra C Harrington","doi":"10.1167/iovs.66.7.6","DOIUrl":"10.1167/iovs.66.7.6","url":null,"abstract":"<p><p>Childhood myopia is a growing global public health concern. Treatments to control myopia are a priority because myopia, particularly high myopia, poses significant lifelong risks of vision loss from myopia-associated ocular pathologies. Intensive research efforts over the past two decades have led to the development of several effective strategies for controlling myopia in children: increased time outdoors, atropine eye drops, dual-focus and multifocal contact lenses, orthokeratology lenses, and specialized spectacle lenses. While the efficacy of these strategies is variable, evidence is growing regarding the potential benefits of applying these interventions in children with myopia, although none completely halt myopia progression. Despite this evidence, dual-focus contact lenses remain the only myopia treatment in the United States approved by the US Food and Drug Administration. This critical review article provides an evidence-based overview of treatment options currently available to prevent the onset of myopia and slow its progression in children. It is the first part of the commissioned paper \"Treatment of Childhood Myopia\" submitted to the National Academies of Sciences, Engineering, and Medicine for the consensus study \"Focus on Myopia-Pathogenesis and Rising Incidence.\" Readers are referred to Part II for a review of treatment mechanisms, emerging and experimental treatments, and patient, treatment, and clinical trial considerations. Findings from this article demonstrate a growing body of strong evidence supporting the use of contemporary treatments in childhood myopia management. Regulatory approvals of these proven treatments worldwide would allow widespread, early intervention in at-risk children and potentially reduce the risk of vision loss from myopia-related complications later in life.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 7","pages":"6"},"PeriodicalIF":5.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225489","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":"Optical and Visual Diet in Myopia.","authors":"Susana Marcos","doi":"10.1167/iovs.66.7.3","DOIUrl":"10.1167/iovs.66.7.3","url":null,"abstract":"<p><p>The alarming increase in myopia prevalence in modern times is attributed to environmental changes affecting young individuals. Visual scenes are projected onto the retina by the eye's optical components and sampled by retinal photoreceptors, shaping the spatial, temporal, and chromatic \"visual diet\" fed to the visual system. These inputs provide essential signaling for proper emmetropization and, in eyes that develop myopia, trigger the cascade of events leading to excessive axial elongation. This article offers foundational components for formulating computational models of myopic eyes and highlights available and needed optical and structural data to construct longitudinal three-dimensional optical eye models in emmetropes and developing myopes. These wide-angle eye models, in both relaxed and accommodated states, will enable understanding of the changes the eye undergoes at myopia onset and potentially allow exploration of cause-effect relationships in myopia development. Age- and refractive-dependent eye models also serve as platforms to test the coupling of novel optical treatments for myopia control with the resulting blur patterns across the retina. Chromatic, spatial, and temporal stimuli are explored as plausible cues for emmetropization. The article also reviews published theories on mechanisms for encoding the sign of defocus and triggering axial elongation. Fully quantitative technologies for ocular geometrical, biometric, and optical evaluation, as well as for monitoring physical features of the environment, are critical for collecting multidimensional data sets that enable predictive models. Given that time spent outdoors is a major factor associated with myopia development, exploring mechanisms that connect light exposure with myopia is paramount. The article also reviews current proposed mechanisms linked to retinal dopaminergic pathways, dysfunction of melanopsin signaling, and disruption of circadian rhythms-factors altered in modern lifestyles by artificial illumination and prolonged use of digital displays. Understanding the interplay between distinct environmental attributes (e.g., light intensity, spatial frequency distribution, blur, spectral characteristics) and the filtering effects of ocular optics will help elucidate pivotal myopiagenic signals and potentially unveil the complex, multifactorial mechanisms relevant for myopia management. Additionally, an annex appended to the article discusses unresolved inquiries and promising research directions in myopia research, drawing from expert insights.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 7","pages":"3"},"PeriodicalIF":5.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225504","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":"Perspectives on Genetic and Environmental Factors in Myopia, Its Prediction, and the Future Direction of Research.","authors":"Katie M Williams, Christopher J Hammond","doi":"10.1167/iovs.66.7.4","DOIUrl":"10.1167/iovs.66.7.4","url":null,"abstract":"<p><p>The dramatic rise in myopia prevalence over the last century is most likely a function of modern-day childhood - a reduction in time spent outdoors and increasing time on near tasks. The widespread use of handheld digital devices, especially in young children, is of concern - both in terms of myopia risk but additionally that excessive use may be linked to sociodemographic factors and could more widely negatively affect health outcomes. Refractive error is a highly heritable trait, and genetic factors are the leading determinant of refractive status variation within a particular environment. Better understanding of these genetic factors could enable prediction of future myopia status, provide novel therapeutic avenues, and personalised treatment. Monitoring axial length growth of increasing interest, likely offering better identification of pre-myopia status and a more accurate correlate of risk of future visual complications. Prediction models are increasing in utility - comprising the aforementioned factors and artificial intelligence within this area is likely to increase. Population-based interventions, such as increased time outdoors, to reduce the incidence and/or slow myopia progression have shown some success, and combined approaches hold future promise. Children developing high myopia at a young age are most at risk of future complications, yet to date are a under researched cohort. Likewise, progression and potential modification of risk in young adults requires more research. The adoption of improved technology into this field to better quantify outdoor exposure and near activities alongside ocular growth, choroidal thickness and peripheral refractive changes in all mentioned cohorts is needed.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 7","pages":"4"},"PeriodicalIF":5.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12161371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225505","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":"Access to Myopia Care in the United States-A Narrative Review.","authors":"Joy Harewood, Melissa Contreras, Kristine Huang, Shelby Johnson, Jingyun Wang","doi":"10.1167/iovs.66.7.5","DOIUrl":"10.1167/iovs.66.7.5","url":null,"abstract":"<p><p>This review describes the evidence related to the burden of myopia and the status of access to myopia care, including detection, treatment, and management, in the United States. It examines the societal impact of myopia, vision screening guidelines from professional organizations, and state mandates on vision screening. Using the Anderson-Newman framework, the review evaluates access to and utilization of myopia care. It identifies knowledge gaps and barriers, offering strategies to improve access to myopia care and management. Improving access to comprehensive myopia management will require collaboration among stakeholders to address research gaps and develop policies that promote equitable access to the detection, treatment, and management of myopia, particularly for populations at high risk of adverse outcomes.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 7","pages":"5"},"PeriodicalIF":5.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12165310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225488","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":"PRMT5 Regulates Senescence in Retinal Ganglion Cells by Targeting the Wnt/β-Catenin Signaling Cascade.","authors":"Yumeng Zhang, Hanwen Huang, Huimin Zhong, Yang Zhang, Siqi He, Yanzhi Guo, Yiwei Wang, Ping Huang, Shouyue Huang, Yisheng Zhong","doi":"10.1167/iovs.66.6.8","DOIUrl":"10.1167/iovs.66.6.8","url":null,"abstract":"<p><strong>Purpose: </strong>In patients with glaucoma, progressive degeneration of retinal ganglion cells (RGCs) leads to irreversible visual impairments. Despite recent studies indicating that senescence is associated with RGC death, the underlying molecular mechanisms remain unclear.</p><p><strong>Methods: </strong>The chronic ocular hypertension (COH) mouse model was established by infusing a crosslinking hydrogel into the anterior chamber. Cellular senescence was evaluated using Western blot analysis, cell cycle, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay, and immunofluorescence. Functional experiments were conducted in retinal precursor (R28) cells through small interfering RNA-mediated knockdown and plasmid-mediated overexpression. Additionally, the role of the protein arginine methyltransferase 5 (PRMT5)-regulated Wnt/β-catenin pathway in RGC senescence was investigated via intravitreal injection of GSK3326595 and CHIR99021 in mice.</p><p><strong>Results: </strong>We demonstrate that PRMT5 is markedly downregulated in RGC in a COH mouse model, correlating with increased RGC senescence induced by elevated intraocular pressure. Silencing PRMT5 significantly accelerated senescence, as evidenced by increased SA-β-gal activity, cell cycle arrest, and senescence marker upregulation. Cotreatment with GSK3β inhibitor CHIR99021 alleviated hypoxia-induced senescence and reactivated the Wnt/β-catenin pathway, while the antagonist FH535 negated the neuroprotective effects of PRMT5 overexpression. In vivo, the PRMT5 inhibitor GSK3326595 reduced RGC survival and heightened senescence markers, whereas CHIR99021 mitigated RGC loss and restored Wnt/β-catenin signaling.</p><p><strong>Conclusions: </strong>Taken together, these findings highlight the critical role of the PRMT5-regulated Wnt/β-catenin pathway in RGC senescence and neurodegeneration. Targeting this pathway represents a promising therapeutic strategy for glaucoma.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"8"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208547","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":"Characterization of Bruch's Membrane Formation in Human Fetal Retina and De Novo Membrane Synthesis by hPSC-Derived Retinal Pigment Epithelium.","authors":"Emily P Lanning, Matthew J Branch, Philippa Harding, Miriam Margari, Alexander J Smith, Robin R Ali, Rachael A Pearson","doi":"10.1167/iovs.66.6.40","DOIUrl":"10.1167/iovs.66.6.40","url":null,"abstract":"<p><strong>Purpose: </strong>Little is known about the development of Bruch's membrane (BrM), the structure separating and supporting the retina and choroid, nor whether differentiation of human pluripotent stem cell (hPSC)-derived retinal pigment epithelium (RPE) accurately replicates BrM. This has relevance for tissue engineering strategies, both in the development of accurate in vitro models, and effective RPE transplant strategies. Here, we investigated BrM-associated protein production in human fetal tissue and hPSC-derived RPE.</p><p><strong>Methods: </strong>The presence of laminin, elastin, fibronectin, and types I/III/IV collagen was examined in human fetal eyes at 6 to 21 post-conception weeks (PCWs) and hPSC-derived RPE cultures at 1 to 6 weeks in culture using immunohistochemistry/immunocytochemistry and quantitative PCR (qPCR).</p><p><strong>Results: </strong>In human fetal retina, laminin and fibronectin were present from 6 PCW, type IV collagen from 8 PCW, elastin from 12 PCW, type I collagen by 17 PCW, and type III collagen from 21 PCW. BrM layering was discernible from 12 PCW, becoming distinct by 17 PCW. In hPSC-derived RPE cultures, basement membranes containing laminin and fibronectin were present from week 1, type IV collagen from week 2, and type I collagen from week 4. Type III collagen was present at all timepoints, although not localized as a basement membrane. Elastin was absent at all timepoints.</p><p><strong>Conclusions: </strong>BrM-like membrane synthesis in hPSC-derived RPE largely recapitulates the temporal sequence seen in human development, excluding elastin. These support the utility of hPSC-derived RPE in in vitro systems to model RPE/retina interactions in health and disease, and inform cell therapy approaches, as de novo BrM-like membrane has the potential to support transplanted donor RPE.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"40"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266234","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":"Erratum in: Ocular Surface Involvements in the Development of Sjögren's Syndrome-Associated Dry Eye in the IL14α Transgenic Mouse.","authors":"","doi":"10.1167/iovs.66.6.39","DOIUrl":"10.1167/iovs.66.6.39","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 6","pages":"39"},"PeriodicalIF":5.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166500/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266235","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}