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Artificial Intelligence-Assisted Matching of Human Postmortem Donors to Ocular Research Projects. 人工智能辅助匹配人眼研究项目的人类死后供体。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_82
Gregory H Grossman, Thomas Cattell, Alyssa Abbott, Daniel MacIntyre
{"title":"Artificial Intelligence-Assisted Matching of Human Postmortem Donors to Ocular Research Projects.","authors":"Gregory H Grossman, Thomas Cattell, Alyssa Abbott, Daniel MacIntyre","doi":"10.1007/978-3-031-76550-6_82","DOIUrl":"10.1007/978-3-031-76550-6_82","url":null,"abstract":"<p><p>The scarcity of human ocular samples with short postmortem intervals (PMIs) is a significant issue in ophthalmic research and drug discovery. A contributing factor is that eye banks must manually match donor data to prospective research project criteria, which is time-consuming, inefficient, and error-prone. We have previously reported on the successful use of a semi-automated matching system, ReSync. The barrier to full autonomy is that donor medical data is often provided as unstructured data in free text fields, which prevents interoperability with matching databases. Herein, we report on a small retrospective study, in which artificial intelligence (AI) is incorporated into ReSync (ReSyncAI) to test AI's ability to structure donor data for subsequent matching. From a set of historical cases, medical data was securely sent to a large language model with natural language processing. After structuring and standardizing, data was returned to ReSync for analysis and match testing. A 94.2% success rate in medical terminology keyword extraction in concert with correcting and standardizing medical data was achieved. Structured data was fully interoperable with ReSync. In a subset of cases, ReSyncAI properly matched donors to the standardized term of \"age-related macular degeneration\" from donor data, including instances of abbreviations, misspellings, and incomplete designations.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"505-509"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Calcium-Binding Protein 4 Is Fundamental for Retinal Structure and Function. 钙结合蛋白4是视网膜结构和功能的基础。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_33
Billie Beckwith-Cohen, Simon M Petersen-Jones
{"title":"Calcium-Binding Protein 4 Is Fundamental for Retinal Structure and Function.","authors":"Billie Beckwith-Cohen, Simon M Petersen-Jones","doi":"10.1007/978-3-031-76550-6_33","DOIUrl":"10.1007/978-3-031-76550-6_33","url":null,"abstract":"<p><p>Calcium-binding proteins (CaBPs) are a subfamily of calmodulin-like proteins, that modulate presynaptic calcium-dependent interactions with voltage-gated calcium channels. CaBPs play crucial roles in the development of normal sensorineural structure and function in both the visual and auditory systems. Disruption of CaBPs can result in a range of synaptic disorders of varying severity, which are dependent on the proteins or isoforms that predominate the affected system. In the retina, CaBP4 seems to be the isoform that is most important for the development of structure and function of the photoreceptor to ON bipolar synapse. Absence of CaBP4 results in synaptic ribbon immaturity in the first retinal synapse, disruption of ON-bipolar cell-driven responses, and a structurally thin outer plexiform layer. It has recently been demonstrated that at least some of the functional and anatomic disruption caused by CaBP mutations can be successfully addressed with gene augmentation therapy both in the eye and ear.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"203-206"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Extracellular Matrix Gene Expression Patterns in Retinal Wound Healing: A Comparative Study Between Mouse and Zebrafish Laser Injury Models. 视网膜创伤愈合中的细胞外基质基因表达模式：小鼠和斑马鱼激光损伤模型的比较研究。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_35
Laura Jahnke, Volker Enzmann
{"title":"Extracellular Matrix Gene Expression Patterns in Retinal Wound Healing: A Comparative Study Between Mouse and Zebrafish Laser Injury Models.","authors":"Laura Jahnke, Volker Enzmann","doi":"10.1007/978-3-031-76550-6_35","DOIUrl":"10.1007/978-3-031-76550-6_35","url":null,"abstract":"<p><p>Fibrosis is an outcome of irregular wound healing, manifesting as heightened scar formation marked by substantial extracellular matrix (ECM) accumulation, persistent inflammation, and gradual tissue or organ restructuring. This condition disrupts the normal tissue architecture, impairing organ function. Herein, the pivotal role of fibrosis in retinal repair mechanisms is compared in mice and zebrafish in responses to laser-induced injury. Our focus spans the intricate interplay between the gene regulation of ECM-involved protagonists and the dynamic development of fibrotic scars. We observed differential gene expression shifts and evaluated the effects of the fibrosis inhibitor pirfenidone (PFD) in the mouse model. These insights into retinal repair mechanisms contribute to a comprehensive understanding, guiding future therapeutic strategies for vision preservation.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"213-217"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Classifying Mouse RPE Morphometric Heterogeneity Using REShAPE: An AI-Based Image Analysis Tool. 使用 REShAPE 对小鼠 RPE 形态异质性进行分类：基于人工智能的图像分析工具
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_65
Davide Ortolan, Dominik Reichert, Huirong Li, Dylan Walmsley, Ruchi Sharma, Kapil Bharti
{"title":"Classifying Mouse RPE Morphometric Heterogeneity Using REShAPE: An AI-Based Image Analysis Tool.","authors":"Davide Ortolan, Dominik Reichert, Huirong Li, Dylan Walmsley, Ruchi Sharma, Kapil Bharti","doi":"10.1007/978-3-031-76550-6_65","DOIUrl":"10.1007/978-3-031-76550-6_65","url":null,"abstract":"<p><p>Retinal degenerative diseases caused by retinal pigment epithelium (RPE) dysfunction affect specific areas of the retina. Regions of molecular and phenotypic RPE heterogeneity have been described in the human eye and are thought to underlie geographic differential RPE sensitivity to degeneration. The mouse is one of the most widely used models to study retinal degeneration. A deeper understanding of mouse RPE heterogeneity can facilitate the interpretation of the observed phenotypes in models of retinal degeneration. In this study, we used an AI-based image analysis algorithm (REShAPE) to generate morphometric maps of RPE flatmounts in young adult mice (2 months old). Using cell area, we distinguished three concentric subpopulations of phenotypic heterogeneity. Treatment with sodium iodate, a widely used oxidative agent to model retinal degenerations, induced RPE atrophy of the two centermost subpopulations. RPE morphometric analysis could prove useful when analyzing animal models of retinal degeneration.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"395-399"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
The Power of Zebrafish in Disease Modeling and Therapy Discovery for Inherited Retinal Degeneration. 斑马鱼在遗传性视网膜变性的疾病建模和疗法探索中的作用。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_38
Huanhuan Xiao, Randi Marshall, Meera T Saxena, Liyun Zhang
{"title":"The Power of Zebrafish in Disease Modeling and Therapy Discovery for Inherited Retinal Degeneration.","authors":"Huanhuan Xiao, Randi Marshall, Meera T Saxena, Liyun Zhang","doi":"10.1007/978-3-031-76550-6_38","DOIUrl":"10.1007/978-3-031-76550-6_38","url":null,"abstract":"<p><p>In the research of inherited retinal degeneration (IRD), zebrafish have emerged as a powerful model system, offering profound insights into disease mechanisms and opening new therapeutic avenues. This mini-review discusses the distinctive advantages that zebrafish provide for investigating retinal degeneration. It outlines contemporary genetic tools, with a specific focus on advanced CRISPR/Cas9 gene targeting technology, utilized for genome manipulation and disease modeling in zebrafish. By emphasizing the pivotal role of zebrafish in large-scale high-throughput drug discovery and the exploration of innovative gene therapy strategies, this succinct review underscores the adaptability and significance of the zebrafish model in advancing IRD research. It establishes a robust foundation for future studies and therapeutic developments in the field.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"229-233"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Uncovering Novel Drugs that Restore Vision Using Orthogonal Pooling in Zebrafish. 利用正交池法在斑马鱼中发现恢复视力的新药。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_80
Justine O'Brien, Patrizia Colucci, Yolanda Alvarez, Breandán N Kennedy
{"title":"Uncovering Novel Drugs that Restore Vision Using Orthogonal Pooling in Zebrafish.","authors":"Justine O'Brien, Patrizia Colucci, Yolanda Alvarez, Breandán N Kennedy","doi":"10.1007/978-3-031-76550-6_80","DOIUrl":"10.1007/978-3-031-76550-6_80","url":null,"abstract":"<p><p>Photoreceptor and retinal pigment epithelium (RPE) dysfunction in inherited retinal degenerations (IRDs) and age-related macular degeneration (AMD) necessitate innovative therapies to preserve vision. Vision impairment incurs a substantial global economic burden, with the World Health Organization reporting an annual global productivity loss of approximately $411 billion. Current treatments are limited, underscoring the urgency for novel solutions. Leveraging new screening techniques, novel drugs restoring vision can be uncovered. Here, a workflow is described utilising orthogonal pooling to screen randomised library compounds for drug hits restoring vision and assessing the optokinetic response (OKR) in the atp6v0e1<sup>-/-</sup> zebrafish model of inherited blindness.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"491-495"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Expression of Versican in the Retina and Its Implication in Retinal Disease. Versican在视网膜中的表达及其在视网膜疾病中的意义。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_69
Andrea E Dillinger, Anja K Hoffmann, Ernst R Tamm
{"title":"Expression of Versican in the Retina and Its Implication in Retinal Disease.","authors":"Andrea E Dillinger, Anja K Hoffmann, Ernst R Tamm","doi":"10.1007/978-3-031-76550-6_69","DOIUrl":"10.1007/978-3-031-76550-6_69","url":null,"abstract":"<p><p>Chondroitin sulfate proteoglycans are characterized by their sulfated glycosaminoglycan chains covalently attached to the core protein. Versican, encoded by the CSPG2 gene, is a chondroitin sulfate proteoglycan highly expressed in the human and mouse retina. Due to alternative splicing, it exists in four different isoforms: V0, V1, V2 and V3. Interactions with a variety of proteins lead to its main functions, such as influencing cellular adhesion, migration, proliferation and regulating inflammatory processes. Versican expression is high during retinal development and decreases in the mature tissue, remaining mostly in the retinal pigment epithelium, Bruch's membrane and choroid blood vessel walls. Mutations in the CSPG2 gene resulting in an imbalance of Versican splice variants cause erosive vitreoretinopathy and Wagner disease. Its regulatory role in a variety of functions, especially those influencing extracellular matrix composition and inflammation, suggests a crucial role in the pathomechanisms of retinal degenerative disorders and should be the purpose of future research.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"423-427"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Frequency and Pattern of Gene Therapy Clinical Trials for Inherited Retinal Diseases. 遗传性视网膜疾病基因治疗临床试验的频率和模式。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_15
Hossein Ameri, Niranjana Kesavamoorthy, Dara N Bruce
{"title":"Frequency and Pattern of Gene Therapy Clinical Trials for Inherited Retinal Diseases.","authors":"Hossein Ameri, Niranjana Kesavamoorthy, Dara N Bruce","doi":"10.1007/978-3-031-76550-6_15","DOIUrl":"10.1007/978-3-031-76550-6_15","url":null,"abstract":"<p><p>This study describes worldwide gene therapy clinical trials aimed at treating inherited retinal diseases (IRD). The information was collected through 15 different international registries including clinicaltrials.gov . There have been 101 gene therapy clinical trials targeting IRD up until the end of 2022. Seventy-seven trials employed gene augmentation using viral vectors; other approaches included inhibitory RNA (9), encapsulated cell technology (6), systemic approach (1), and observational trials (8). The most common clinical trial phase was phase 1/2 (46), followed by phase 3 (12). One trial led to an FDA-approved treatment. Sixty-nine trials were conducted in a single country, and 32 trials were multinational; The USA had the highest share in both categories. Retinitis pigmentosa was the most common disease targeted (39), followed by RPE65-mediated retinal dystrophy (13), Leber hereditary optic neuropathy (13), choroideremia (10 and achromatopsia (8), Leber congenital amaurosis (4), X-linked retinoschisis (4), Stargardt disease (4), Bietti's crystalline dystrophy (2), autosomal dominant optic atrophy (1), and Gyrate atrophy (1). For gene augmentation trials, adeno-associated virus was the most commonly used viral vector (70 trials-90%).</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"89-93"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Interplay of Retinal and Choroidal Vasculatures in Ocular Health and Disease. 视网膜和脉络膜血管在眼部健康和疾病中的相互作用。
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_75
Albert L Gonzales, Alexa Paikai, David Maeng
{"title":"Interplay of Retinal and Choroidal Vasculatures in Ocular Health and Disease.","authors":"Albert L Gonzales, Alexa Paikai, David Maeng","doi":"10.1007/978-3-031-76550-6_75","DOIUrl":"10.1007/978-3-031-76550-6_75","url":null,"abstract":"<p><p>The eye, a complex sensory organ, integrates the cornea, lens, and choroid to focus light onto retinal photoreceptor cells, converting light into electrical signals for visual interpretation. This intricate process is vital for human perception, enabling navigation, object recognition, and a rich visual experience. The circulatory system plays a crucial role in delivering nutrients, O<sub>2</sub>, and removing waste from cells, contributing to intraocular pressure regulation and maintaining eye structure. Photoreceptors, highly metabolically demanding cells, rely on retinal and choroidal vasculatures for O<sub>2</sub> and nutrients. This chapter emphasizes structural and functional distinctions between retinal and choroidal vasculature, exploring their implications in the pathophysiological development of diverse retinal degenerative diseases.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"459-463"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Is Caveolin-1 Required for Retinal Neuroprotection? 视网膜神经保护需要小窝蛋白-1吗？
4区 医学
Advances in experimental medicine and biology Pub Date : 2025-01-01 DOI: 10.1007/978-3-031-76550-6_47
Olawale O Bankole, Michael H Elliott
{"title":"Is Caveolin-1 Required for Retinal Neuroprotection?","authors":"Olawale O Bankole, Michael H Elliott","doi":"10.1007/978-3-031-76550-6_47","DOIUrl":"10.1007/978-3-031-76550-6_47","url":null,"abstract":"<p><p>The innate ability to produce neurotrophic cytokines is a crucial component of retinal neuroprotection. Reduced levels of these cytokines accelerate neuronal cell death in the retina during injury but prolonged overexpression can lead to inflammation and retinal damage. It is therefore critical to find molecular targets that regulate the endogenous production of retinal neurotrophic factors. Outside of the eye, caveolins play essential roles in preconditioning, pro-survival signaling, and neuronal protection. They amplify the secretion of neuroprotective cytokines such as leukemia inhibitory factor (LIF), an important retinal neurotroph. We hypothesize that Caveolin-1 (Cav1) in the retina is required for retinal neuroprotection. This mini-review summarizes findings on the cytoprotective roles of Cav1 and how it may be required for retinal neuroprotection.</p>","PeriodicalId":7270,"journal":{"name":"Advances in experimental medicine and biology","volume":"1468 ","pages":"287-291"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
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